Occurrence of Chiral Bioactive Compounds in the Aquatic Environment: A Review
---
paper_title: Risk assessment of the endocrine-disrupting effects of nine chiral pesticides

paper_content:

The increased release of chiral pesticides into the environment has generated interest in the role of enantioselectivity in the environmental fate and ecotoxicological effects of these compounds. However, the information on the endocrine disrupting effects (EDEs) of chiral pesticides is still limited and discrepancies are also usually observed among different assays. In this study, we investigated the enantioselectivity of EDEs via estrogen and thyroid hormone receptors for nine chiral pesticides using in vitro and in silico approaches. The results of the luciferase reporter gene assays showed 7 chiral pesticides possessed enantioselective estrogenic activities and 2 chiral pesticides exerted thyroid hormone antagonistic effects. Proliferation assays in MCF-7 and GH3 cells were also used to verify the results of the dual-luciferase reporter gene assays. At last, the molecular docking results indicated that the enantioselective EDEs of chiral pesticides were partially due to enantiospecific binding affinities with receptors. Our data not only show enantioselective EDEs of nine chiral pesticides, but also would be helpful to better understanding the molecular biological mechanisms of enantioselectivity in EDEs of chiral pesticides.
---
paper_title: Selective degradation of ibuprofen and clofibric acid in two model river biofilm systems

paper_content:

Abstract A field survey indicated that the Elbe and Saale Rivers were contaminated with both clofibric acid and ibuprofen. In Elbe River water we could detect the metabolite hydroxy-ibuprofen. Analyses of the city of Saskatoon sewage effluent discharged to the South Saskatchewan river detected clofibric acid but neither ibuprofen nor any metabolite. Laboratory studies indicated that the pharmaceutical ibuprofen was readily degraded in a river biofilm reactor. Two metabolites were detected and identified as hydroxy–and carboxy–ibuprofen. Both metabolites were observed to degrade in the biofilm reactors. However, in human metabolism the metabolite carboxy–ibuprofen appears and degrades second whereas the opposite occurs in biofilm systems. In biofilms the pharmacologically inactive stereoisomere of ibuprofen is degraded predominantly. In contrast, clofibric acid was not biologically degraded during the experimental period of 21 days. Similar results were obtained using biofilms developed using waters from either the South Saskatchewan or Elbe River. In a sterile reactor no losses of ibuprofen were observed. These results suggested that abiotic losses and adsorption played only a minimal role in the fate of the pharmaceuticals in the river biofilm reactors.
---
paper_title: Enantiomeric composition of chiral polychlorinated biphenyl atropisomers in aquatic bed sediment.

paper_content:

Enantiomeric ratios (ERs) for eight polychlorinated biphenyl (PCB) atropisomers were measured in aquatic sediment from selected sites throughout the United States by using chiral gas chromatography/mass spectrometry. Nonracemic ERs for PCBs 91, 95, 132, 136, 149, 174, and 176 were found in sediment cores from Lake Hartwell, SC, which confirmed previous inconclusive reports of reductive dechlorination of PCBs at these sites on the basis of achiral measurements. Nonracemic ERs for many of the atropisomers were also found in bed-sediment samples from the Hudson and Housatonic Rivers, thus indicating that some of the PCB biotransformation processes identified at these sites are enantioselective. Patterns in ERs among congeners were consistent with known reductive dechlorination patterns at both river sediment basins. The enantioselectivity of PCB 91 is reversed between the Hudson and Housatonic River sites, which implies that the two sites have different PCB biotransformation processes with different enantiom...
---
paper_title: Persistent organic pollutants in China's surface water systems.

paper_content:

Following recent rapid industrialization, China is now one of the largest producers and consumers of organic chemicals in the world. This is compounded by variable regulatory oversight with respect to storage, use and waste management of these chemicals and their byproducts. This review synthesizes the data on the distribution of selected persistent organic pollutants (POPs) in waters in China. Surface water heavily polluted with POPs is distributed in the Yangtze River Estuary, Pearl River Delta, Minjiang River Estuary, Jiulongjiang Estuary, Daya Bay, Taihu Lake, and the waterways of Zhejiang Province, where concentrations of Polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) frequently exceed both international and Chinese guideline values. These areas are mainly distributed along the southeast coast of China, within or downstream of major manufacturing districts, intensive agricultural basins, and other industrial centers. A comparison of the levels of OCPs in the aquatic environment of China with other indicative regions worldwide shows comparable levels of pollution (overall range from below detection limit (BDL) to 5104.8ng/L and regional means from 2.9-929.6ng/L). PAHs and PCBs pollution appear to be particularly serious in China (PAHs overall ranging from BDL to 474,000ng/L with regional means from 15.1-72,400ng/L; PCBs from BDL to 3161ng/L with regional means ranging from 0.2-985.2ng/L). There is as yet limited evidence of serious perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) pollution. We discuss major sources and processes responsible for high POP occurrence using a range of measures (including diagnostic ratios of different compounds), regulatory oversight and policy gaps in the control of POPs in China, and potential long-term health and ecological effects. We argue that water quality guidelines, pollution control measures and cleanup strategies for POPs in China should be urgently improved.
---
paper_title: Concentrations, enantiomeric compositions, and sources of HCH, DDT and chlordane in soils from the Pearl River Delta, South China.

paper_content:

Concentrations, and enantiomeric compositions of HCH, DDT and chlordane in 74 soils of the Pearl River Delta, South China were investigated. The mean concentrations of HCHs and DDTs descended in the order: crop soils>paddy soils>natural soils. The concentrations (ng/g dw) of p,p'-DDE, p,p'-DDT, p,p'-DDD and o,p'-DDT in crop soils were 0.14-231, 0.07-315, <DL-96.7 and 0.06-73.8, respectively, while those of chlordane were generally below 0.78 for trans-chlordane (TC) and 0.75 for cis-chlordane (CC). Enantiomeric factors (EF value) were determined for o,p'-DDT, alpha-HCH, TC and CC. Both preferential depletions of (-) enantiomer and (+) enantiomer were observed for o,p'-DDT and alpha-HCH, indicated by EF values either <0.5 or >0.5. An EF value >0.5 generally suggested a preferential degradation of the (-) enantiomers of both TC and CC. The racemic alpha-HCH observed in the soils with higher HCH concentrations indicated that the transformation from gamma-HCH (e.g. lindane) to alpha-HCH may be an important process in the soils. The isomer ratios of p,p'-DDT/(DDE+DDD), o,p'-DDT/p,p'-DDT and enantiomeric compositions of o,p'-DDT suggested that both illegal use of technical DDT and the DDT impurity in dicofol may be responsible for the freshly DDT input in the region. The sources of DDTs were drawn by principal component analysis-multiple linear regression (PCA-MLR). The relative contributions of dicofol-type DDT, residues, and fresh technical DDT were estimated to be 55%, 21% and 17%, respectively. In addition, CC was found to degraded faster than TC in soils from the Pearl River Delta. The study demonstrated that the combination of isomer ratios and enantiomeric composition analysis may provide critical information on the potential sources and fate of organochlorine pesticides in soil.
---
paper_title: Enantioselective degradation of warfarin in soils

paper_content:

Environmental enantioselectivity information is important to fate assessment of chiral contaminants. Warfarin, a rodenticide and prescription medicine, is a chiral chemical but used in racemic form. Little is known about its enantioselective behavior in the environment. In this study, enantioselective degradation of warfarin in a turfgrass and a groundcover soils was examined in aerobic and ambient temperature conditions. An enantioselective analytical method was established using a novel triproline chiral stationary phase in high performance liquid chromatography. Unusual peak profile patterns, i.e., first peak (S(−)) broadening/second peak (R(+)) compression with hexane (0.1%TFA)/2-propanol (92/8, v/v) mobile phase, and first peak compression/second peak broadening with the (96/4, v/v) mobile phase, were observed in enantioseparation. This unique tunable peak property was leveraged in evaluating warfarin enantioselective degradation in two types of soil. Warfarin was extracted in high recovery from soil using methylene chloride after an aqueous phase basic-acidic conversion. No apparent degradation of warfarin was observed in the sterile turfgrass and groundcover soils during the 28 days incubation, while it showed quick degradation (half-life <7 days) in the nonsterile soils after a short lag period, suggesting warfarin degradation in the soils was mainly caused by micro-organisms. Limited enantioselectivity was found in the both soils, which was the R(+) enantiomer was preferentially degraded. The half-lives in turfgrass soil were 5.06 ± 0.13 and 5.97 ± 0.05 days, for the R(+) and the S(−) enantiomer, respectively. The corresponding values for the groundcover soil were 4.15 ± 0.11 and 4.47 ± 0.08 days. Chirality, 2011. © 2011 Wiley Periodicals, Inc.
---
paper_title: Enantioselectivity in environmental risk assessment of modern chiral pesticides.

paper_content:

Chiral pesticides comprise a new and important class of environmental pollutants nowadays. With the development of industry, more and more chiral pesticides will be introduced into the market. But their enantioselective ecotoxicology is not clear. Currently used synthetic pyrethroids, organophosphates, acylanilides, phenoxypropanoic acids and imidazolinones often behave enantioselectively in agriculture use and they always pose unpredictable enantioselective ecological risks on non-target organisms or human. It is necessary to explore the enantioselective toxicology and ecological fate of these chiral pesticides in environmental risk assessment. The enantioselective toxicology and the fate of these currently widely used pesticides have been discussed in this review article.
---
paper_title: Prioritizing research for trace pollutants and emerging contaminants in the freshwater environment.

paper_content:

Organic chemicals have been detected at trace concentrations in the freshwater environment for decades. Though the term trace pollutant indicates low concentrations normally in the nanogram or microgram per liter range, many of these pollutants can exceed an acceptable daily intake (ADI) for humans. Trace pollutants referred to as emerging contaminants (ECs) have recently been detected in the freshwater environment and may have adverse human health effects. Analytical techniques continue to improve; therefore, the number and frequency of detections of ECs are increasing. It is difficult for regulators to restrict use of pollutants that are a human health hazard; scientists to improve treatment techniques for higher priority pollutants; and the public to modify consumption patterns due to the vast number of ECs and the breadth of literature on the occurrence, use, and toxicity. Hence, this paper examines literature containing occurrence and toxicity data for three broad classes of trace pollutants and ECs (industrials, pesticides, and pharmaceuticals and personal care products (PPCPs)), and assesses the relevance of 71 individual compounds. The evaluation indicates that widely used industrials (BPF) and PPCPs (AHTN, HHCB, ibuprofen, and estriol) occur frequently in samples from the freshwater environment but toxicity data were not available; thus, it is important to establish their ADI. Other widely used industrials (BDE-47, BDE-99) and pesticides (benomyl, carbendazim, aldrin, endrin, ethion, malathion, biphenthrin, and cypermethrin) have established ADI values but occurrence in the freshwater environment was not well documented. The highest priority pollutants for regulation and treatment should include industrials (PFOA, PFOS and DEHP), pesticides (diazinon, methoxychlor, and dieldrin), and PPCPs (EE2, carbamazepine, βE2, DEET, triclosan, acetaminophen, and E1) because they occur frequently in the freshwater environment and pose a human health hazard at environmental concentrations.
---
paper_title: Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms

paper_content:

Here presented for the first time is the enantioselective biodegradation of amphetamine and methamphetamine in river microcosm bioreactors. The aim of this investigation was to test the hypothesis that mechanisms governing the fate of amphetamine and methamphetamine in the environment are mostly stereoselective and biological in nature. Several bioreactors were studied over the duration of 15 days (i) in both biotic and abiotic conditions, (ii) in the dark or exposed to light and (iii) in the presence or absence of suspended particulate matter. Bioreactor samples were analysed using SPE-chiral-LC-(QTOF)MS methodology. This investigation has elucidated the fundamental mechanism for degradation of amphetamine and methamphetamine as being predominantly biological in origin. Furthermore, stereoselectivity and changes in enantiomeric fraction (EF) were only observed under biotic conditions. Neither amphetamine nor methamphetamine appeared to demonstrate adsorption to suspended particulate matter. Our experiments also demonstrated that amphetamine and methamphetamine were photo-stable. Illicit drugs are present in the environment at low concentrations but due to their pseudo-persistence and non-racemic behaviour, with two enantiomers revealing significantly different potency (and potentially different toxicity towards aquatic organisms) the risk posed by illicit drugs in the environment should not be under- or over-estimated. The above results demonstrate the need for re-evaluation of the procedures utilised in environmental risk assessment, which currently do not recognise the importance of the phenomenon of chirality in pharmacologically active compounds.
---
paper_title: Environmental Fate of Chiral Pharmaceuticals: Determination, Degradation and Toxicity

paper_content:

Pollution of the aquatic environment by pharmaceuticals is of major concern. Indeed pharmaceutical pollutants have several undesirable effects for many organisms, such as endocrine disruption and bacterium resistance. They are resistant to several degradation processes, making their removal difficult and slow. Pharmaceuticals reach the environment due to their inefficient removal by waste water treatment plants (WWTP), and by improper disposal of unused medicines. In aquatic environments pharmaceuticals reach concentrations at trace levels of ngL−1–μgL−1 range. Many pharmaceutical pollutants are chiral. They occur in nature as a single enantiomer or as mixtures of the two enantiomers, which have different spatial configuration and can thus be metabolized selectively. In spite of similar physical and chemical properties, enantiomers have different interactions with enzymes, receptors or other chiral molecules, leading to different biological response. Therefore they can affect living organisms in a different manner. The fate and effects of enantiomers of chiral pharmaceuticals in the environment are still largely unknown. Biodegradation and toxicity can be enantioselective, in contrast to abiotic degradation. Thus accurate methods to measure enantiomeric fractions in the environment are crucial to better understand the biodegradation process and to estimate toxicity of chiral pharmaceuticals. We review (1) general properties of chiral compounds, (2) current knowledge on chiral pharmaceuticals in the environment, (3) chiral analytical methods to determine the enantiomers composition in environmental matrices, (4) degradation and removal processes of chiral pharmaceuticals in the environment and (5) their toxicity to aquatic organisms. The major analytical methods discussed are gas chromatography (GC), high performance liquid chromatography (HPLC), electrochemical sensors and biosensors. These chiral methods are crucial for the correct quantification of the enantiomers regarding that if an enantiomer with more or less toxic effects is preferentially degraded, the assessed exposure based on measurements of achiral methodologies would overestimate or underestimate ecotoxicity. The degradation and biodegradation is discussed using few examples of important therapeutic classes usually detected in the aquatic environment. Few examples of ecotoxicity studies are also given on the occurrence of enantiomers and their fate in the environment which differs with regard to undesirable effects and to biochemical processes.
---
paper_title: Metabolism studies of chiral pesticides: A critical review

paper_content:

Abstract The consumption of pesticides worldwide has been growing in recent decades, and consequently the exposure of humans and other animals to them as well. However, even though it is known that chiral pesticides can behave stereoselectively, the knowledge about the risks to human health and the environment is scarce. Among the pesticides registered to date, approximately 30% have at least one center of asymmetry, and just 7% of them are currently marketed as a pure stereoisomer or as an enriched mixture of the active stereoisomer. There are several in vitro , in vivo , and in silico models available to evaluate the enantioselective metabolism of chiral pesticides aiming ecotoxicological and risk assessment. Therefore, this paper intends to provide a critical view of the metabolism of chiral pesticides in non-target species, including humans, and discuss their implications, as well as, conduct a review of the analytical techniques employed for in vitro and in vivo metabolism studies of chiral pesticides.
---
paper_title: Occurrence and removal of organic micropollutants: An overview of the watch list of EU Decision 2015/495.

paper_content:

Although there are no legal discharge limits for micropollutants into the environment, some regulations have been published in the last few years. Recently, a watch list of substances for European Union-wide monitoring was reported in the Decision 2015/495/EU of 20 March 2015. Besides the substances previously recommended to be included by the Directive 39/2013/EU, namely two pharmaceuticals (diclofenac and the synthetic hormone 17-alpha-ethinylestradiol (EE2)) and a natural hormone (17-beta-estradiol (E2)), the first watch list of 10 substances/groups of substances also refers three macrolide antibiotics (azithromycin, clarithromycin and erythromycin), other natural hormone (estrone (E1)), some pesticides (methiocarb, oxadiazon, imidacloprid, thiacloprid, thiamethoxam, clothianidin, acetamiprid and triallate), a UV filter (2-ethylhexyl-4-methoxycinnamate) and an antioxidant (2,6-di-tert-butyl-4-methylphenol) commonly used as food additive. Since little is known about the removal of most of the substances included in the Decision 2015/495/EU, particularly regarding realistic concentrations in aqueous environmental samples, this review aims to: (i) overview the European policy in the water field; (ii) briefly describe the most commonly used conventional and advanced treatment processes to remove micropollutants; (iii) summarize the relevant data published in the last decade, regarding occurrence and removal in aqueous matrices of the 10 substances/groups of substances that were recently included in the first watch list for European Union monitoring (Decision 2015/495/EU); and (iv) highlight the lack of reports concerning some substances of the watch list, the study of un-spiked aquatic matrices and the assessment of transformation by-products.
---
paper_title: Chiral Analysis of Pesticides and Drugs of Environmental Concern: Biodegradation and Enantiomeric Fraction

paper_content:

The importance of stereochemistry for medicinal chemistry and pharmacology is well recognized and the dissimilar behavior of enantiomers is fully documented. Regarding the environment, the significance is equivalent since enantiomers of chiral organic pollutants can also differ in biodegradation processes and fate, as well as in ecotoxicity. This review comprises designed biodegradation studies of several chiral drugs and pesticides followed by enantioselective analytical methodologies to accurately measure the enantiomeric fraction (EF). The enantioselective monitoring of microcosms and laboratory-scale experiments with different environmental matrices is herein reported. Thus, this review focuses on the importance of evaluating the EF variation during biodegradation studies of chiral pharmaceuticals, drugs of abuse, and agrochemicals and has implications for the understanding of the environmental fate of chiral pollutants.
---
paper_title: Priority Substances and Emerging Organic Pollutants in Portuguese Aquatic Environment: A Review.

paper_content:

Aquatic environments are among the most noteworthy ecosystems regarding chemical pollution due to the anthropogenic pressure. In 2000, the European Commission implemented the Water Framework Directive, with the aim of progressively reducing aquatic chemical pollution of the European Union countries. Therefore, the knowledge about the chemical and ecological status is imperative to determine the overall quality of water bodies. Concerning Portugal, some studies have demonstrated the presence of pollutants in the aquatic environment but an overall report is not available yet. The aim of this paper is to provide a comprehensive review about the occurrence of priority substances included in the Water Framework Directive and some classes of emerging organic pollutants that have been found in Portuguese aquatic environment. The most frequently studied compounds comprise industrial compounds, natural and synthetic estrogens, phytoestrogens, phytosterols, pesticides, pharmaceuticals and personal care products. Concentration of these pollutants ranged from few ng L(-1) to higher values such as 30 μg L(-1) for industrial compounds in surface waters and up to 106 μg L(-1) for the pharmaceutical ibuprofen in wastewaters. Compounds already banned in Europe such as atrazine, alkylphenols and alkylphenol polyethoxylates are still found in surface waters, nevertheless their origin is still poorly understood. Beyond the contamination of the Portuguese aquatic environment by priority substances and emerging organic pollutants, this review also highlights the need of more research on other classes of pollutants and emphasizes the importance of extending this research to other locations in Portugal, which have not been investigated yet.
---
paper_title: Enantioselective HPLC analysis and biodegradation of atenolol, metoprolol and fluoxetine

paper_content:

The accurate quantification of enantiomers is crucial for assessing the biodegradation of chiral pharmaceuticals in the environment. Methods to quantify enantiomers in environmental matrices are scarce. Here, we used an enantioselective method, high-performance liquid chromatography with fluorescence detection (HPLC-FD), to analyze two beta-blockers, metoprolol and atenolol, and the antidepressant fluoxetine in an activated sludge consortium from a wastewater treatment plant. The vancomycin-based chiral stationary phase was used under polar ionic mode to achieve the enantioseparation of target chiral pharmaceuticals in a single chromatographic run. The method was successfully validated over a concentration range of 20–800 ng/mL for each enantiomer of both beta-blockers and of 50–800 ng/mL for fluoxetine enantiomers. The limits of detection were between 5 and 20 ng/mL and the limits of quantification were between 20 and 50 ng/mL, for all enantiomers. The intra- and inter-batch precision was lower than 5.66 and 8.37 %, respectively. Accuracy values were between 103.03 and 117.92 %, and recovery rates were in the range of 88.48–116.62 %. Furthermore, the enantioselective biodegradation of atenolol, metoprolol and fluoxetine was followed during 15 days. The (S)-enantiomeric form of metoprolol was degraded at higher extents, whereas the degradation of atenolol and fluoxetine did not show enantioselectivity under the applied conditions.
---
paper_title: Stereochemistry of organic compounds

paper_content:

Structure Stereoisomers Symmetry Configuration Properties of Stereoisomers: Stereoisomer Discrimination Separation of Stereoisomers, Resolution, Racemization Heterotopic Ligands and Faces (Prostereoisomerism, Prochirality) Stereochemistry of Alkenes Conformation of Acyclic Molecules Configuration and Conformation of Cyclic Molecules Stereoselective Synthesis Chiroptical Properties Chirality in Molecules Devoid of Chiral Centres.
---
paper_title: Removal of fluoxetine and its effects in the performance of an aerobic granular sludge sequential batch reactor.

paper_content:

Fluoxetine (FLX) is a chiral fluorinated pharmaceutical mainly indicated for treatment of depression and is one of the most distributed drugs. There is a clear evidence of environmental contamination with this drug. Aerobic granular sludge sequencing batch reactors constitute a promising technology for wastewater treatment; however the removal of carbon and nutrients can be affected by micropollutants. In this study, the fate and effect of FLX on reactor performance and on microbial population were investigated. FLX adsorption/desorption to the aerobic granules was observed. FLX shock loads (≤4μM) did not show a significant effect on the COD removal. Ammonium removal efficiency decreased in the beginning of first shock load, but after 20 days, ammonia oxidizing bacteria became adapted. The nitrite concentration in the effluent was practically null indicating that nitrite oxidizing bacteria was not inhibited, whereas, nitrate was accumulated in the effluent, indicating that denitrification was affected. Phosphate removal was affected at the beginning showing a gradual adaptation, and the effluent concentration was <0.04mM after 70 days. A shift in microbial community occurred probably due to FLX exposure, which induced adaptation/restructuration of the microbial population. This contributed to the robustness of the reactor, which was able to adapt to the FLX load.
---
paper_title: Effects of Engineered Nanoparticles on the Enantioselective Transformation of Metalaxyl Agent and Commercial Metalaxyl in Agricultural Soils.

paper_content:

The adsorption coefficient of racemic metalaxyl onto an agriculture soil was small and nonenantioselective. Biotransformation was the predominant pathway for the elimination of R-metalaxyl, while abiotic and biotransformation made a comparable contribution to the degradation of S-metalaxyl. Metalaxyl acid was the main transformation intermediate. The enantiomer fraction of metalaxyl decreased with an increase in its initial spike concentration or the presence of the co-constituents in metalaxyl commercial products. Under simulated solar irradiation, the presence of TiO2 promoted the overall transformation kinetics through enhanced biotransformation and extra photoinduced chemical reactions. The promotion was enantioselective and thereafter changed the enantiomer fraction. The results obtained in this study showed that some achiral parameters, although they have no direct impact on enantioselective reactions with enantiomers, can significantly affect the enantioselective transformation of racemic metalaxyl. Thus, our results indicate that the contribution of chemical interactions on the enantioselective transformation of chiral pesticides may be underestimated.
---
paper_title: Unequal Activities of Enantiomers via Biological Receptors: Examples of Chiral Drug, Pesticide, and Fragrance Molecules

paper_content:

A molecule coming from outside an organism can form a ligand–receptor complex. Upon its formation, a message is transmitted, for example, to certain cells. In this way, two enantiomers can emit messages that differ, either quantitatively or qualitatively. In the present article, these facts are taken as a common basis for the actions of chiral drug, pesticide, and fragrance molecules. For each of these groups, a few examples of current interest were selected. At present, the demand for single enantiomers in medicine and agriculture is economically highly significant. We propose a two-hour lecture, emphasizing the similarity between the different types of receptor-mediated actions of enantiomers, thus connecting some seemingly unrelated subjects in the university curricula. The lecture is intended for medicinal chemistry students; in addition, it should be suitable for the third-year chemistry students who are interested in the applications presented here.
---
paper_title: Homochiral drugs: a demanding tendency of the pharmaceutical industry.

paper_content:

The issue of drug chirality is now a major theme in the design and development of new drugs, underpinned by a new understanding of the role of molecular recognition in many pharmacologically relevant events. In general, three methods are utilized for the production of a chiral drug: the chiral pool, separation of racemates, and asymmetric synthesis. Although the use of chiral drugs predates modern medicine, only since the 1980's has there been a significant increase in the development of chiral pharmaceutical drugs. An important commercial reason is that as patents on racemic drugs expire, pharmaceutical companies have the opportunity to extend patent coverage through development of the chiral switch enantiomers with desired bioactivity. Stimulated by the new policy statements issued by the regulatory agencies, the pharmaceutical industry has systematically begun to develop chiral drugs in enantiometrically enriched pure forms. This new trend has caused a tremendous change in the industrial small- and large-scale production to enantiomerically pure drugs, leading to the revisiting and updating of old technologies, and to the development of new methodologies of their large-scale preparation (as the use of stereoselective syntheses and biocatalyzed reactions). The final decision whether a given chiral drug will be marketed in an enantiomerically pure form, or as a racemic mixture of both enantiomers, will be made weighing all the medical, financial and social proficiencies of one or other form. The kinetic, pharmacological and toxicological properties of individual enantiomers need to be characterized, independently of a final decision.
---
paper_title: Treatment of a simulated wastewater amended with a chiral pharmaceuticals mixture by an aerobic granular sludge sequencing batch reactor

paper_content:

Abstract An aerobic granular sludge-sequencing batch reactor (AGS-SBR) was fed for 28-days with a simulated wastewater containing a mixture of chiral pharmaceuticals (CPs) (alprenolol, bisoprolol, metoprolol, propranolol, venlafaxine, salbutamol, fluoxetine and norfluoxetine), each at 1.3 μg L −1 . AGS-SBR exhibited the highest removal efficiency for norfluoxetine, with preferential removal of the ( R )-enantiomer indicating that biological-mediated processes occurred. For all other CPs, removal was non-enantioselective, occurring through biosorption onto AGS. A gradual decline of CPs removal was observed, probably related to the decrease of AGS adsorption capacity. Moreover, chemical oxygen demand (COD) content in the bulk liquid after anaerobic feeding increased, and P-release dropped, probably because the polyphosphate-accumulating organism's activity was affected. Nitrification was also affected as indicated by the ammonium effluent concentration increase. Moreover, CPs exposure promoted AGS disintegration, with decreasing granule size. After stopping CPs feeding, the AGS started to recover its compact structure, and the system returned its normal performance concerning COD- and P-removal. N-removal seemed to be a more sensitive process, as while the ammonium levels were fully restored at the end of operation, nitrite reduction was only partially restored. Results provide useful information on AGS performance during the treatment of wastewater containing pharmaceuticals, a frequent scenario in WWTP.
---
paper_title: Mathematical model and experimental validation of the synergistic effect of selective enantioseparation of (S)-amlodipine from pharmaceutical wastewater using a HFSLM

paper_content:

Abstract A case study on the synergistic enantioseparation of ( S )-amlodipine from pharmaceutical wastewater by using hollow fiber supported liquid membrane (HFSLM) was examined. A chiral reaction flux mathematical model was applied. Optimum conditions achieved the highest percentages of extraction and stripping viz. 84% and 80%, respectively. Relevant parameters affecting the enantioseparation efficiency of ( S )-amlodipine were determined. Standard deviation percentages were 2.31% for extraction and 1.26% for stripping. It was found that the mathematical model proved to be in good agreement with the experimental data.
---
paper_title: Enantioselective biodegradation of pharmaceuticals, alprenolol and propranolol, by an activated sludge inoculum.

paper_content:

Biodegradation of chiral pharmaceuticals in the environment can be enantioselective. Thus quantification of enantiomeric fractions during the biodegradation process is crucial for assessing the fate of chiral pollutants. This work presents the biodegradation of alprenolol and propranolol using an activated sludge inoculum, monitored by a validated enantioselective HPLC method with fluorescence detection. The enantioseparation was optimized using a vancomycin-based chiral stationary phase under polar ionic mode. The method was validated using a minimal salts medium inoculated with activated sludge as matrix. The method was selective and linear in the range of 10-800 ng/ml, with a R²>0.99. The accuracy ranged from 85.0 percent to 103 percent, the recovery ranged from 79.9 percent to 103 percent, and the precision measured by the relative standard deviation (RSD) was <7.18 percent for intra-batch and <5.39 percent for inter-batch assays. The limits of quantification and detection for all enantiomers were 10 ng/ml and 2.5 ng/ml, respectively. The method was successfully applied to follow the biodegradation of the target pharmaceuticals using an activated sludge inoculum during a fifteen days assay. The results indicated slightly higher biodegradation rates for the S-enantiomeric forms of both beta-blockers. The presence of another carbon source maintained the enantioselective degradation pattern while enhancing biodegradation extent up to fourteen percent.
---
paper_title: Enantioselectivity in environmental risk assessment of modern chiral pesticides.

paper_content:

Chiral pesticides comprise a new and important class of environmental pollutants nowadays. With the development of industry, more and more chiral pesticides will be introduced into the market. But their enantioselective ecotoxicology is not clear. Currently used synthetic pyrethroids, organophosphates, acylanilides, phenoxypropanoic acids and imidazolinones often behave enantioselectively in agriculture use and they always pose unpredictable enantioselective ecological risks on non-target organisms or human. It is necessary to explore the enantioselective toxicology and ecological fate of these chiral pesticides in environmental risk assessment. The enantioselective toxicology and the fate of these currently widely used pesticides have been discussed in this review article.
---
paper_title: Integrated liquid chromatography method in enantioselective studies: Biodegradation of ofloxacin by an activated sludge consortium.

paper_content:

Ofloxacin is a chiral fluoroquinolone commercialized as racemate and as its enantiomerically pure form levofloxacin. This work presents an integrated liquid chromatography (LC) method with fluorescence detection (FD) and exact mass spectrometry (EMS) developed to assess the enantiomeric biodegradation of ofloxacin and levofloxacin in laboratory-scale microcosms. The optimized enantioseparation conditions were achieved using a macrocyclic antibiotic ristocetin A-bonded CSP (150×2.1mm i.d.; particle size 5μm) under reversed-phase elution mode. The method was validated using a mineral salts medium as matrix and presented selectivity and linearity over a concentration range from 5μgL(-1) (quantification limit) to 350μgL(-1) for each enantiomer. The method was successfully applied to evaluate biodegradation of ofloxacin enantiomers at 250μgL(-1) by an activated sludge inoculum. Ofloxacin (racemic mixture) and (S)-enantiomer (levofloxacin) were degraded up to 58 and 52%, respectively. An additional degradable carbon source, acetate, enhanced biodegradation up to 23%. (S)-enantiomer presented the highest extent of degradation (66.8%) when ofloxacin was supplied along with acetate. Results indicated slightly higher biodegradation extents for the (S)-enantiomer when supplementation was done with ofloxacin. Degradation occurred faster in the first 3days and proceeded slowly until the end of the assays. The chromatographic results from LC-FD suggested the formation of the (R)-enantiomer during levofloxacin biodegradation which was confirmed by LC-MS with a LTQ Orbitrap XL.
---
paper_title: Organic Stereochemistry: Guiding Principles and Bio-Medicinal Relevance

paper_content:

Foreword: D. Seebach Preface: The Editors Part 1: Symmetry Elements and Operations, Classification of Stereoisomers (B. Testa, G. Vistoli, and A. Pedretti) Part 2: Stereoisomerism Resulting from One or Several Stereogenic Centers (B. Testa) Part 3: Other Stereogenic Elements: Axes of Chirality, Planes of Chirality, Helicity, and (E,Z)-Diastereoisomerism (B. Testa) Part 4: Isomerisms about Single Bonds and in Cyclic Systems (B. Testa, G. Vistoli, and A. Pedretti) Part 5: Stereoselectivity in Molecular and Clinical Pharmacology (B. Testa, G. Vistoli, A. Pedretti, and J. Caldwell) Part 6: The Conformation Factor in Molecular Pharmacology (G. Vistoli, B. Testa, and A. Pedretti) Part 7: The Concept of Substrate Stereoselectivity in Biochemistry and Xenobiotic Metabolism (B. Testa) Part 8: Prostereoisomerism and the Concept of Product Stereoselectivity in Biochemistry and Xenobiotic Metabolism (B. Testa) Part 9: Molecular Chirality in Chemistry and Biology: Historical Milestones (J. Gal) Glossary Index
---
paper_title: Influence of pH on the Stereoselective Degradation of the Fungicides Epoxiconazole and Cyproconazole in Soils

paper_content:

Many pesticides are chiral and consist of two or more enantiomers/stereoisomers, which may differ in biological activity, toxicity, effects on nontarget organisms, and environmental fate. In the last few years, several racemic compounds have been substituted by enantiomer-enriched or single-isomer compounds (“chiral switch”). In this context, the stereoselective degradation in soils is an important part of a benefit−risk evaluation, but the understanding of the environmental factors affecting the chiral preferences is limited. In this study, the stereoselective degradation of the fungicides epoxiconazole and cyproconazole was investigated in different soils, selected to cover a wide range of soil properties. The fungicides were incubated under laboratory conditions and the degradation and configurational stability of the stereoisomers were followed over time using enantioselective GC−MS with a γ-cyclodextrin derivative as chiral selector. In alkaline and slightly acidic soils, the degradation of epoxicona...
---
paper_title: Environmental Fate of Chiral Pharmaceuticals: Determination, Degradation and Toxicity

paper_content:

Pollution of the aquatic environment by pharmaceuticals is of major concern. Indeed pharmaceutical pollutants have several undesirable effects for many organisms, such as endocrine disruption and bacterium resistance. They are resistant to several degradation processes, making their removal difficult and slow. Pharmaceuticals reach the environment due to their inefficient removal by waste water treatment plants (WWTP), and by improper disposal of unused medicines. In aquatic environments pharmaceuticals reach concentrations at trace levels of ngL−1–μgL−1 range. Many pharmaceutical pollutants are chiral. They occur in nature as a single enantiomer or as mixtures of the two enantiomers, which have different spatial configuration and can thus be metabolized selectively. In spite of similar physical and chemical properties, enantiomers have different interactions with enzymes, receptors or other chiral molecules, leading to different biological response. Therefore they can affect living organisms in a different manner. The fate and effects of enantiomers of chiral pharmaceuticals in the environment are still largely unknown. Biodegradation and toxicity can be enantioselective, in contrast to abiotic degradation. Thus accurate methods to measure enantiomeric fractions in the environment are crucial to better understand the biodegradation process and to estimate toxicity of chiral pharmaceuticals. We review (1) general properties of chiral compounds, (2) current knowledge on chiral pharmaceuticals in the environment, (3) chiral analytical methods to determine the enantiomers composition in environmental matrices, (4) degradation and removal processes of chiral pharmaceuticals in the environment and (5) their toxicity to aquatic organisms. The major analytical methods discussed are gas chromatography (GC), high performance liquid chromatography (HPLC), electrochemical sensors and biosensors. These chiral methods are crucial for the correct quantification of the enantiomers regarding that if an enantiomer with more or less toxic effects is preferentially degraded, the assessed exposure based on measurements of achiral methodologies would overestimate or underestimate ecotoxicity. The degradation and biodegradation is discussed using few examples of important therapeutic classes usually detected in the aquatic environment. Few examples of ecotoxicity studies are also given on the occurrence of enantiomers and their fate in the environment which differs with regard to undesirable effects and to biochemical processes.
---
paper_title: Analytical separation of enantiomers by gas chromatography on chiral stationary phases.

paper_content:

Enantioselective GC is of widespread use in the enantiomeric analysis of volatile natural products such as pheromones, flavors, fragrances, and essential oils as well as synthetic products obtained from asymmetric syntheses and kinetic resolutions. Whereas enantioseparation of derivatized α-amino acids is performed on chiral stationary phases (CSPs) based on α-amino acid derivatives, alkylated/acylated cyclodextrins are employed as versatile CSPs for a multitude of volatile derivatized and nonderivatized enantiomers. Three main types of CSPs are reviewed and the miniaturization of enantioselective GC, the quantification of enantiomers, and validation issues are described. A list of commercially available fused silica capillary columns coated with various CSPs is compiled.
---
paper_title: Evolution of chiral stationary phase design in the Pirkle laboratories

paper_content:

An historical review of the design of chiral stationary phases (CSPs) in the Pirkle laboratories is presented. Beginning with the discovery of the non-equivalence of nuclear magnetic resonance signals arising from enantiomers in the presence of a chiral solvating agent more than 25 years ago the Pirkle group has been at the forefront of the study of the enantioselective interactions of chiral molecules. Dozens of CSPs have been synthesized and evaluated, and several of these CSPs have subsequently been commercialized and are now widely used by researchers around the world. Several recently developed CSPs are also presented, and general principles which have guided the design of these CSPs are discussed.
---
paper_title: Solid-phase extraction combined with dispersive liquid-liquid microextraction and chiral liquid chromatography-tandem mass spectrometry for the simultaneous enantioselective determination of representative proton-pump inhibitors in water samples

paper_content:

This report describes, for the first time, the simultaneous enantioselective determination of proton-pump inhibitors (PPIs-omeprazole, lansoprazole, pantoprazole, and rabeprazole) in environmental water matrices based on solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME) and chiral liquid chromatography-tandem mass spectrometry. The optimized results of SPE-DLLME were obtained with PEP-2 column using methanol-acetonitrile (1/1, v/v) as elution solvent, dichloroethane, and acetonitrile as extractant and disperser solvent, respectively. The separation and determination were performed using reversed-phase chromatography on a cellulose chiral stationary phase, a Chiralpak IC (250 mm × 4.6 mm, 5 μm) column, under isocratic conditions at 0.6 mL min(-1) flow rate. The analytes were detected in multiple reaction monitoring (MRM) mode by triple quadrupole mass spectrometry. Isotopically labeled internal standards were used to compensate matrix interferences. The method provided enrichment factors of around 500. Under optimal conditions, the mean recoveries for all eight enantiomers from the water samples were 89.3-107.3 % with 0.9-10.3 % intra-day RSD and 2.3-8.1 % inter-day RSD at 20 and 100 ng L(-1) levels. Correlation coefficients (r (2)) ≥ 0.999 were achieved for all enantiomers within the range of 2-500 μg L(-1). The method detection and quantification limits were at very low levels, within the range of 0.67-2.29 ng L(-1) and 2.54-8.68 ng L(-1), respectively. This method was successfully applied to the determination of the concentrations and enantiomeric fractions of the targeted analytes in wastewater and river water, making it applicable to the assessment of the enantiomeric fate of PPIs in the environment. Graphical Abstract Simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.
---
paper_title: Assessment of the pharmaceutical active compounds removal in wastewater treatment systems at enantiomeric level. Ibuprofen and naproxen.

paper_content:

The enantioselective degradation of ibuprofen and naproxen enantiomers was evaluated in five different wastewater treatment systems, including three constructed wetlands (vertical- and horizontal-flow configurations), a sand filter and an activated sludge wastewater treatment plant. In addition, injection experiments were carried out with racemic ibuprofen at microcosm- and pilot-scale constructed wetlands. Ibuprofen and naproxen have an asymmetric carbon atom and, consequently, two enantiomeric forms (i.e. S and R). The enantiomeric fraction (EF=S/(S+R)) in the raw sewage and effluents of various wastewater treatments were found to be compound-dependent (i.e. ibuprofen: EF(influent)=0.73-0.90, EF(effluent)=0.60-0.76; naproxen: EF(influent)=0.88-0.90, EF(effluent)=0.71-0.86). Of the two chiral pharmaceuticals, naproxen was the only one whose effluent EF correlated with its removal efficiency (p<0.05). The lack of correlation found for ibuprofen was attributable to the fact that its enantioselective degradation kinetics were different under prevailing aerobic and anaerobic conditions. Injection experiments of ibuprofen in constructed wetlands at microcosm and pilot-scale followed similar trends. Hence, under prevailing aerobic conditions, S-ibuprofen degraded faster than R-ibuprofen, whereas under prevailing anaerobic conditions, the degradation was not enantioselective. In summary, the naproxen EF measurements in wastewater effluents show that naproxen is a suitable alternative for evaluating the removal efficiency of treatment systems because its enantioselective degradation is similar under prevailing aerobic and anaerobic conditions.
---
paper_title: Enantioselective HPLC analysis and biodegradation of atenolol, metoprolol and fluoxetine

paper_content:

The accurate quantification of enantiomers is crucial for assessing the biodegradation of chiral pharmaceuticals in the environment. Methods to quantify enantiomers in environmental matrices are scarce. Here, we used an enantioselective method, high-performance liquid chromatography with fluorescence detection (HPLC-FD), to analyze two beta-blockers, metoprolol and atenolol, and the antidepressant fluoxetine in an activated sludge consortium from a wastewater treatment plant. The vancomycin-based chiral stationary phase was used under polar ionic mode to achieve the enantioseparation of target chiral pharmaceuticals in a single chromatographic run. The method was successfully validated over a concentration range of 20–800 ng/mL for each enantiomer of both beta-blockers and of 50–800 ng/mL for fluoxetine enantiomers. The limits of detection were between 5 and 20 ng/mL and the limits of quantification were between 20 and 50 ng/mL, for all enantiomers. The intra- and inter-batch precision was lower than 5.66 and 8.37 %, respectively. Accuracy values were between 103.03 and 117.92 %, and recovery rates were in the range of 88.48–116.62 %. Furthermore, the enantioselective biodegradation of atenolol, metoprolol and fluoxetine was followed during 15 days. The (S)-enantiomeric form of metoprolol was degraded at higher extents, whereas the degradation of atenolol and fluoxetine did not show enantioselectivity under the applied conditions.
---
paper_title: Use of the chiral pharmaceutical propranolol to identify sewage discharges into surface waters.

paper_content:

The discharge of relatively small volumes of untreated sewage is a source of wastewater-derived contaminants in surface waters that is often ignored because it is difficult to discriminate from wastewater effluent. To identify raw sewage discharges, we analyzed the two enantiomers of the popular chiral pharmaceutical, propranolol, after derivitization to convert the enantiomers to diastereomers. The enantiomeric fraction (the ratio of the concentration of one of its isomers to the total concentration) of propranolol in the influent of five wastewater treatment plants was 0.50 +/- 0.02, while after secondary treatment it was 0.42 or less. In a laboratory study designed to simulate an activated sludge municipal wastewater treatment system, the enantiomeric fraction of propranolol decreased from 0.5 to 0.43 as the compound underwent biotransformation. In a similar system designed to simulate an effluent-dominanted surface water, the enantiomeric fraction of propranolol remained constant as it underwent biotransformation. Analysis of samples from surface waters with known or suspected discharges of untreated sewage contained propranolol with an enantiomeric fraction of approximately 0.50 whereas surface waters with large discharges of wastewater effluent contained propranolol with enantiomeric fractions similar to those observed in wastewater effluent. Measurement of enantiomers of propranolol may be useful in detecting and documenting contaminants related to leaking sewers and combined sewer overflows.
---
paper_title: Tutorial review on validation of liquid chromatography-mass spectrometry methods: part II.

paper_content:

This is the part II of a tutorial review intending to give an overview of the state of the art of method validation in liquid chromatography mass spectrometry (LC-MS) and discuss specific issues that arise with MS (and MS-MS) detection in LC (as opposed to the "conventional" detectors). The Part II starts with briefly introducing the main quantitation methods and then addresses the performance related to quantification: linearity of signal, sensitivity, precision, trueness, accuracy, stability and measurement uncertainty. The last section is devoted to practical considerations in validation. With every performance characteristic its essence and terminology are addressed, the current status of treating it is reviewed and recommendations are given, how to handle it, specifically in the case of LC-MS methods.
---
paper_title: Enantiomeric determination of chiral persistent organic pollutants and their metabolites

paper_content:

Many persistent organic pollutants (POPs) are chiral and are generally released into the environment as racemates, but frequently undergo alterations in enantiomeric composition as soon as they are subjected to biochemical processes. Enantiospecific analysis of chiral POPs is important, since enantiomers of chiral compounds often exhibit differences in biological activity, and most biochemical processes in nature are stereospecific. The effects and the environmental fate of the enantiomers of chiral pollutants therefore need to be investigated separately. Chiral separation of enantiomers is one of the most challenging tasks for any analytical technique. We discuss different aspects of enantiospecific analysis of chiral POPs, including classical POPs and their metabolites, as well as some emerging POPs.
---
paper_title: Enantioselective determination of representative profens in wastewater by a single-step sample treatment and chiral liquid chromatography-tandem mass spectrometry.

paper_content:

This manuscript describes, for the first time, the simultaneous enantioselective determination of ibuprofen, naproxen and ketoprofen in wastewater based on liquid chromatography tandem mass spectrometry (LC-MS/MS). The method uses a single-step sample treatment based on microextraction with a supramolecular solvent made up of hexagonal inverted aggregates of decanoic acid, formed in situ in the wastewater sample through a spontaneous self-assembly process. Microextraction of profens was optimized and the analytical method validated. Isotopically labeled internal standards were used to compensate for both matrix interferences and recoveries. Apparent recoveries for the six enantiomers in influent and effluent wastewater samples were in the interval 97-103%. Low method detection limits (MDLs) were obtained (0.5-1.2 ng L(-1)) as a result of the high concentration factors achieved in the microextraction process (i.e. actual concentration factors 469-736). No analyte derivatization or evaporation of extracts, as it is required with GC-MS, was necessary. Relative standard deviations for enantiomers in wastewater were always below 8%. The method was applied to the determination of the concentrations and enantiomeric fractions of the targeted analytes in influents and effluents from three wastewater treatment plants. All the values found for profen enantiomers were consistent with those previously reported and confirmed again the suitability of using the enantiomeric fraction of ibuprofen as an indicator of the discharge of untreated or poorly treated wastewaters. Both the analytical and operational features of this method make it applicable to the assessment of the enantiomeric fate of profens in the environment.
---
paper_title: Field and laboratory studies of the fate and enantiomeric enrichment of venlafaxine and O-desmethylvenlafaxine under aerobic and anaerobic conditions.

paper_content:

The stereoselectivity of R,S-venlafaxine and its metabolites R,S-O-desmethylvenlafaxine, N-desmethylvenlafaxine, O,N-didesmethylvenlafaxine, N,N-didesmethylvenlafaxine and tridesmethylvenlafaxine was studied in three processes: (i) anaerobic and aerobic laboratory scale tests; (ii) six wastewater treatment plants (WWTPs) operating under different conditions; and (iii) a variety of wastewater treatments including conventional activated sludge, natural attenuation along a receiving river stream and storage in operational and seasonal reservoirs. In the laboratory and field studies, the degradation of the venlafaxine yielded O-desmethylvenalfaxine as the dominant metabolite under aerobic and anaerobic conditions. Venlafaxine was almost exclusively converted to O-desmethylvenlafaxine under anaerobic conditions, but only a fraction of the drug was transformed to O-desmethylvenlafaxine under aerobic conditions. Degradation of venlafaxine involved only small stereoisomeric selectivity. In contrast, the degradation of O-desmethylvenlafaxine yielded remarkable S to R enrichment under aerobic conditions but none under anaerobic conditions. Determination of venlafaxine and its metabolites in the WWTPs agreed well with the stereoselectivity observed in the laboratory studies. Our results suggest that the levels of the drug and its metabolites and the stereoisomeric enrichment of the metabolite and its parent drug can be used for source tracking and for discrimination between domestic and nondomestic wastewater pollution. This was indeed demonstrated in the investigations carried out at the Jerusalem WWTP.
---
paper_title: Enantioselective simultaneous analysis of selected pharmaceuticals in environmental samples by ultrahigh performance supercritical fluid based chromatography tandem mass spectrometry.

paper_content:

In order to assess the true impact of each single enantiomer of pharmacologically active compounds (PACs) in the environment, highly efficient, fast and sensitive analytical methods are needed. For the first time this paper focuses on the use of ultrahigh performance supercritical fluid based chromatography coupled to a triple quadrupole mass spectrometer to develop multi-residue enantioselective methods for chiral PACs in environmental matrices. This technique exploits the advantages of supercritical fluid chromatography, ultrahigh performance liquid chromatography and mass spectrometry. Two coated modified 2.5 μm-polysaccharide-based chiral stationary phases were investigated: an amylose tris-3,5-dimethylphenylcarbamate column and a cellulose tris-3-chloro-4-methylphenylcarbamate column. The effect of different chromatographic variables on chiral recognition is highlighted. This novel approach resulted in the baseline resolution of 13 enantiomers PACs (aminorex, carprofen, chloramphenicol, 3-N-dechloroethylifosfamide, flurbiprofen, 2-hydroxyibuprofen, ifosfamide, imazalil, naproxen, ofloxacin, omeprazole, praziquantel and tetramisole) and partial resolution of 2 enantiomers PACs (ibuprofen and indoprofen) under fast-gradient conditions (<10 min analysis time). The overall performance of the methods was satisfactory. The applicability of the methods was tested on influent and effluent wastewater samples. To the best of our knowledge, this is the first feasibility study on the simultaneous separation of chemically diverse chiral PACs in environmental matrices using ultrahigh performance supercritical fluid based chromatography coupled with tandem mass spectrometry.
---
paper_title: Enantiomeric Profiling of Chiral Drugs in Wastewater and Receiving Waters

paper_content:

The aim of this paper is to discuss the enantiomer-specific fate of chiral drugs during wastewater treatment and in receiving waters. Several chiral drugs were studied: amphetamine-like drugs of abuse (amphetamine, methamphetamine, MDMA, MDA), ephedrines (ephedrine and pseudoephedrine), antidepressant venlafaxine, and beta-blocker atenolol. A monitoring program was undertaken in 7 WWTPs (utilizing mainly activated sludge and trickling filters technologies) and at 6 sampling points in receiving waters over the period of 9 months. The results revealed the enantiomer-specific fate of all studied drugs during both wastewater treatment and in the aqueous environment. The extent of stereoselectivity depended on several parameters including: type of chiral drug (high stereoselectivity was recorded for atenolol and MDMA), treatment technology used (activated sludge showed higher stereoselectivity than trickling filters), and season (higher stereoselectivity was observed in the aqueous environment over the spring/...
---
paper_title: Gas chromatographic enantioseparation of chiral pollutants—techniques and results

paper_content:

Publisher Summary This chapter discusses the enantioseparation of chiral pollutants through gas chromatography technique. The phenomenon of enantioselective processes for a certain chiral pollutant in the environment can be compared with its interaction with different chiral stationary phases (CSPs). On one CSP, the enantiomers are resolved, and on the next, they are not. On one CSP the (+)-enantiomer elutes second (interacts more with the CSP), on another CSP the (+)-enantiomer elutes first. Prerequisite for enantioseparation is the interaction of the enantiomers with another chiral system followed by the formation of associations that behave like diastereomers. The most complex point is the interpretation of the data that aims to generalize the findings. To obtain knowledge from the result, one should know the meaning of measured EFs in a general content. Nevertheless, studies and approaches such as, using EF determinations in closed but complex systems such as sewage treatment plants, is a promising tool to find out more about the fate of chemicals therein. Despite all uncertainties in EF data, the positive aspects prevail, and the determination of EFs in environmental samples is today, by far more than the addition of a new parameter to monitoring data. The data compiled in this article may be helpful for stimulating new studies and eliciting some hidden aspects of this acknowledged field of research.
---
paper_title: Selective degradation of ibuprofen and clofibric acid in two model river biofilm systems

paper_content:

Abstract A field survey indicated that the Elbe and Saale Rivers were contaminated with both clofibric acid and ibuprofen. In Elbe River water we could detect the metabolite hydroxy-ibuprofen. Analyses of the city of Saskatoon sewage effluent discharged to the South Saskatchewan river detected clofibric acid but neither ibuprofen nor any metabolite. Laboratory studies indicated that the pharmaceutical ibuprofen was readily degraded in a river biofilm reactor. Two metabolites were detected and identified as hydroxy–and carboxy–ibuprofen. Both metabolites were observed to degrade in the biofilm reactors. However, in human metabolism the metabolite carboxy–ibuprofen appears and degrades second whereas the opposite occurs in biofilm systems. In biofilms the pharmacologically inactive stereoisomere of ibuprofen is degraded predominantly. In contrast, clofibric acid was not biologically degraded during the experimental period of 21 days. Similar results were obtained using biofilms developed using waters from either the South Saskatchewan or Elbe River. In a sterile reactor no losses of ibuprofen were observed. These results suggested that abiotic losses and adsorption played only a minimal role in the fate of the pharmaceuticals in the river biofilm reactors.
---
paper_title: Attenuation of wastewater-derived contaminants in an effluent-dominated river.

paper_content:

Although wastewater-derived chemical contaminants undergo transformation through a variety of mechanisms, the relative importance of processes such as biotransformation and photolysis is poorly understood under conditions representative of large rivers. To assess attenuation rates under conditions encountered in such systems, samples from the Trinity River were analyzed for a suite of wastewater-derived contaminants during a period when wastewater effluent accounted for nearly the entire flow of the river over a travel time of approximately 2 weeks. While the concentration of total adsorbable organic iodide, a surrogate for recalcitrant X-ray phase contrast media in wastewater, was approximately constant throughout the river, concentrations of ethylenediamine tetraacetate, gemfibrozil, ibuprofen, metoprolol, and naproxen all decreased between 60% and 90% as the water flowed downstream. Comparison of attenuation rates estimated in the river with rates measured in laboratory-scale microcosms suggests that biotransformation was more important than photolysis for most of the compounds. Further evidence for biotransformation in the river was provided by measurements of the enantiomeric fraction of metoprolol, which showed a gradual decrease as the water moved downstream. Results of this study indicate that natural attenuation can result in significant decreases in concentrations of wastewater-derived contaminants in large rivers.
---
paper_title: Chiral recognition by enantioselective liquid chromatography: Mechanisms and modern chiral stationary phases

paper_content:

Abstract An overview of the state-of-the-art in LC enantiomer separation is presented. This tutorial review is mainly focused on mechanisms of chiral recognition and enantiomer distinction of popular chiral selectors and corresponding chiral stationary phases including discussions of thermodynamics, additivity principle of binding increments, site-selective thermodynamics, extrathermodynamic approaches, methods employed for the investigation of dominating intermolecular interactions and complex structures such as spectroscopic methods (IR, NMR), X-ray diffraction and computational methods. Modern chiral stationary phases are discussed with particular focus on those that are commercially available and broadly used. It is attempted to provide the reader with vivid images of molecular recognition mechanisms of selected chiral selector–selectand pairs on basis of solid-state X-ray crystal structures and simulated computer models, respectively. Such snapshot images illustrated in this communication unfortunately cannot account for the molecular dynamics of the real world, but are supposed to be helpful for the understanding. The exploding number of papers about applications of various chiral stationary phases in numerous fields of enantiomer separations is not covered systematically.
---
paper_title: Analysis of the chiral pollutants by chromatography

paper_content:

Many organic environmental pollutants are mixtures of their chiral isomers. Studies have revealed that these isomers have different enantioselective distribution, metabolism and toxicity. Today, analysis of chiral pollutants represents an urgent need. This review discusses the analysis of chiral pollutants using gas chromatography (GC), high performance liquid chromatography (HPLC), capillary electro-chromatography (CEC), micellar electrokinetic chromatography (MEKC), super critical fluid chromatography (SFC) and thin layer chromatography (TLC).
---
paper_title: Critical evaluation of monitoring strategy for the multi-residue determination of 90 chiral and achiral micropollutants in effluent wastewater.

paper_content:

It is essential to monitor the release of organic micropollutants from wastewater treatment plants (WWTPs) for developing environmental risk assessment and assessing compliance with legislative regulation. In this study the impact of sampling strategy on the quantitative determination of micropollutants in effluent wastewater was investigated. An extended list of 90 chiral and achiral micropollutants representing a broad range of biological and physico-chemical properties were studied simultaneously for the first time. During composite sample collection micropollutants can degrade resulting in the under-estimation of concentration. Cooling collected sub-samples to 4°C stabilised ≥81 of 90 micropollutants to acceptable levels (±20% of the initial concentration) in the studied effluents. However, achieving stability for all micropollutants will require an integrated approach to sample collection (i.e., multi-bottle sampling with more than one stabilisation method applied). Full-scale monitoring of effluent revealed time-paced composites attained similar information to volume-paced composites (influent wastewater requires a sampling mode responsive to flow variation). The option of monitoring effluent using time-paced composite samplers is advantageous as not all WWTPs have flow controlled samplers or suitable sites for deploying portable flow meters. There has been little research to date on the impact of monitoring strategy on the determination of chiral micropollutants at the enantiomeric level. Variability in wastewater flow results in a dynamic hydraulic retention time within the WWTP (and upstream sewerage system). Despite chiral micropollutants being susceptible to stereo-selective degradation, no diurnal variability in their enantiomeric distribution was observed. However, unused medication can be directly disposed into the sewer network creating short-term (e.g., daily) changes to their enantiomeric distribution. As enantio-specific toxicity is observed in the environment, similar resolution of enantio-selective analysis to more routinely applied achiral methods is needed throughout the monitoring period for accurate risk assessment.
---
paper_title: Enantiomeric analysis of polycyclic musks in water by chiral gas chromatography-tandem mass spectrometry.

paper_content:

Galaxolide (HHCB), tonalide (AHTN), phantolide (AHDI), traseolide (ATII) and cashmeran (DPMI) are synthetic polycyclic musks (PCMs). They are all commonly used in fragrance industries as racemic mixtures. A sensitive and robust enantioselective analytical method was developed to facilitate measurement of these chemicals in wastewater and environmental samples. The method is based on gas chromatography with tandem mass spectrometry (GC-MS/MS). Enantioseparation was assessed using four commercially available chiral capillary columns. Optimised resolution was achieved using a dual-column configuration of a chiral heptakis(2,3- di-O-methyl-6-O-t-butyl dimethylsilyl)-β-cyclodextrin column combined with a (non-chiral) HP-5MS column. This configuration was demonstrated to be capable of effectively resolving all commercially manufactured enantiomers of these five PCMs. Method detection limits for single enantiomers in drinking water and surface water range between 1.01 and 2.39ngL(-1). Full validation of the application of this method in these aqueous matrices is provided.
---
paper_title: Role of Chirality and Macroring in Imprinted Polymers with Enantiodiscriminative Power

paper_content:

Enantioselective discrimination of chiral amines is of great importance as their biological properties often differ. Therefore, here we report the development of synthetic receptors for their enantioselective recognition and pH-sensitive drug release. This paper reports the preparation of three pyridine and two benzene derivatives containing an allyloxy group [(S,S)-5, 6–9] as well as their evaluation as functional monomer anchors for chiral imprinting of amines. The enantiomeric enriching ability and controlled release of the imprinted polymers (IPs) were evaluated using racemic mixture of 1-(1-naphthyl)ethylamine hydrogen perchlorate (1). The effect of the enantiomeric purity of the template on the enantioseparation performance was investigated. Racemic template in combination with enantiomerically pure macrocyclic anchors and vice versa yields IPs with excellent enantiomeric recognition. In vitro drug delivery, enantiomeric enrichment and pH-sensitive release were investigated through kinetic models.
---
paper_title: Chiral profiling of azole antifungals in municipal wastewater and recipient rivers of the Pearl River Delta, China

paper_content:

Enantiomeric compositions and fractions (EFs) of three chiral imidazole (econazole, ketoconazole, and miconazole) and one chiral triazole (tebuconazole) antifungals were investigated in wastewater, river water, and bed sediment of the Pearl River Delta, South China. The imidazole pharmaceuticals in the untreated wastewater were racemic to weakly nonracemic (EFs of 0.450-0.530) and showed weak enantioselectivity during treatment in the sewage treatment plant. The EFs of the dissolved azole antifungals were usually different from those of the sorbed azoles in the suspended particulate matter, suggesting different behaviors for the enantiomers of the chiral azole antifungals in the dissolved and particulate phases of the wastewater. The azole antifungals were widely present in the rivers. The bed sediment was a sink for the imidazole antifungals. The imidazoles were prevalently racemic, whereas tebuconazole was widely nonracemic in the rivers. Seasonal effects were observed on distribution and chirality of the azole antifungals. Concentrations of the azole antifungals in the river water were relatively higher in winter than in spring and summer while the EF of miconazole in the river water was higher in summer. The mechanism of enantiomeric behavior of the chiral azole antifungals in the environment warrants further research.
---
paper_title: Synthesis and Preliminary Structural and Binding Characterization of New Enantiopure Crown Ethers Containing an Alkyl Diarylphosphinate or a Proton-Ionizable Diarylphosphinic Acid Unit

paper_content:

New enantiopure crown ethers containing either an ethyl diarylphosphinate moiety [(S,S)-4 to (S,S)-7] or a proton-ionizable diarylphosphinic acid unit [(S,S)-8 to (S,S)-11] have been synthesized. Electronic circular dichroism (ECD) studies on the complexation of these new enantiopure crown ethers with the enantiomers of α-(1-naphthyl)ethylammonium perchlorate (1-NEA) and with α-(2-naphthyl)ethylammonium perchlorate (2-NEA) were also carried out. These studies showed appreciable enantiomeric recognition with heterochiral [(S,S)-crown ether plus either (R)-1- or (R)-2-NEA] preference. Theoretical calculations found three significant intermolecular hydrogen bonds in the complexes of (S,S)-9. Furthermore, preference for heterochiral complexes was also observed, in good agreement with ECD results. Complex formation constants were determined by NMR titration for four selected crown ether/NEA pairs.
---
paper_title: Enantiomer separation of polychlorinated biphenyl atropisomers and polychlorinated biphenyl retention behavior on modified cyclodextrin capillary gas chromatography columns.

paper_content:

Abstract Seven commercially-available chiral capillary gas chromatography columns containing modified cyclodextrins were evaluated for their ability to separate enantiomers of the 19 stable chiral polychlorinated biphenyl (PCB) atropisomers, and for their ability to separate these enantiomers from achiral congeners, necessary for trace environmental analysis of chiral PCBs. The enantiomers of each of the 19 chiral PCBs were at least partially separated on one or more of these columns. Enantiomeric ratios of eleven atropisomers could also be quantified on six columns as they did not coelute with any other congener containing the same number of chlorine atoms, so could be quantified using gas chromatography–mass spectrometry. Analysis of a lake sediment heavily contaminated with PCBs showed enantioselective occurrence of PCB 91, proof positive of enantioselective in situ reductive dechlorination at the sampling site.
---
paper_title: Occurrence and Behavior of Pesticides in Rainwater, Roof Runoff, and Artificial Stormwater Infiltration

paper_content:

To prevent overloading of sewer systems and to ensure sufficient recharging of the groundwater underneath sealed urban areas, collection and artificial infiltration of roof runoff water has become very popular in many countries including Switzerland. However, there is still a considerable lack of knowledge concerning the quality of roof runoff, particularly with respect to the presence of pesticides. In this work, the occurrence and the temporal variations in concentration in rainwater and in roof runoff from different types of roofs (i.e., clay tile roofs, polyester roofs, flat gravel roofs) were determined for the most important members of three widely used classes of pesticides (i.e., triazines, acetamides, phenoxy acids). It is shown that in rain and roof runoff, maximum pesticide concentrations originating primarily from agricultural use occurred during and right after the application periods. Maximum average concentrations for single rain events and total loads per year were, for example, for atrazi...
---
paper_title: Using chiral liquid chromatography quadrupole time-of-flight mass spectrometry for the analysis of pharmaceuticals and illicit drugs in surface and wastewater at the enantiomeric level.

paper_content:

This paper presents and compares for the first time two chiral LC-QTOF-MS methodologies (utilising CBH and Chirobiotic V columns with cellobiohydrolase and vancomycin as chiral selectors) for the quantification of amphetamine, methamphetamine, MDA (methylenedioxyamphetamine), MDMA (methylenedioxymethamphetamine), propranolol, atenolol, metoprolol, fluoxetine and venlafaxine in river water and sewage effluent. The lowest MDLs (0.3-5.0 ng L(-1) and 1.3-15.1 ng L(-1) for river water and sewage effluent respectively) were observed using the chiral column Chirobiotic V. This is with the exception of methamphetamine and MDMA which had lower MDLs using the CBH column. However, the CBH column resulted in better resolution of enantiomers (R(s)=2.5 for amphetamine compared with R(s)=1.2 with Chirobiotic V). Method recovery rates were typically >80% for both methodologies. Pharmaceuticals and illicit drugs detected and quantified in environmental samples were successfully identified using MS/MS confirmation. In sewage effluent, the total beta-blocker concentrations of propranolol, atenolol and metoprolol were on average 77.0, 1091.0 and 3.6 ng L(-1) thus having EFs (Enantiomeric Fractions) of 0.43, 0.55 and 0.54 respectively. In river water, total propranolol and atenolol was quantified on average at <10.0 ng L(-1). Differences in EF between sewage and river water matrices were evident: venlafaxine was observed with respective EF of 0.43 ± 0.02 and 0.58 ± 0.02.
---
paper_title: Comparative HPLC methods for β-blockers separation using different types of chiral stationary phases in normal phase and polar organic phase elution modes. Analysis of propranolol enantiomers in natural waters.

paper_content:

Abstract The enantioselectivities of β-blockers (propranolol, metoprolol, atenolol and pindolol) on four different types of chiral stationary phases (CSPs): Chiralpak AD-H, Lux Cellulose-1, Chirobiotic T and Sumichiral OA-4900 were compared using polar organic (PO) elution mode and normal phase (NP) elution mode. Method optimizations were demonstrated by modifying parameters such as organic modifier composition (ethanol, 2-propanol and acetonitrile) and basic mobile phase additives (triethylamine, diethylamine, ethanolamine, and buthylamine). In normal phase elution mode with Lux Cellulose-1, the four pairs of enantiomers can be separated in the same run in gradient elution mode. Additionally, a simple chiral HPLC–DAD method using a newly commercialized polysaccharide-based CSP by Phenomenex (Lux Cellulose-1) in NP elution mode for enantioselective determination of propranolol in water samples by highly selective molecularly imprinted polymers extraction was validated. The optimized conditions were a mobile phase composed by n -hexane/ethanol/DEA (70/30/0.3, v/v/v) at a flow rate of 1.0 mL min −1 and 25 °C. The method is selective, precise and accurate and was found to be linear in the range of 0.125–50 μg mL −1 ( R 2 > 0.999) with a method detection limit (MLD) of 0.4 μg mL −1 for both enantiomers. Recoveries achieved with both enantiomers ranged from 97 to 109%.
---
paper_title: Multi-residue enantiomeric analysis of pharmaceuticals and their active metabolites in the Guadalquivir River basin (South Spain) by chiral liquid chromatography coupled with tandem mass spectrometry

paper_content:

This paper describes the development and application of a multi-residue chiral liquid chromatography coupled with tandem mass spectrometry method for simultaneous enantiomeric profiling of 18 chiral pharmaceuticals and their active metabolites (belonging to several therapeutic classes including analgesics, psychiatric drugs, antibiotics, cardiovascular drugs and β-agonists) in surface water and wastewater. To the authors' knowledge, this is the first time an enantiomeric method including such a high number of pharmaceuticals and their metabolites has been reported. Some of the pharmaceuticals have never been studied before in environmental matrices. Among them are timolol, betaxolol, carazolol and clenbuterol. A monitoring programme of the Guadalquivir River basin (South Spain), including 24 sampling sites and five wastewater treatment plants along the basin, revealed that enantiomeric composition of studied pharmaceuticals is dependent on compound and sampling site. Several compounds such as ibuprofen, atenolol, sotalol and metoprolol were frequently found as racemic mixtures. On the other hand, fluoxetine, propranolol and albuterol were found to be enriched with one enantiomer. Such an outcome might be of significant environmental relevance as two enantiomers of the same chiral compound might reveal different ecotoxicity. For example, propranolol was enriched with S(-)-enantiomer, which is known to be more toxic to Pimephales promelas than R(+)-propranolol. Fluoxetine was found to be enriched with S(+)-enantiomer, which is more toxic to P. promelas than R(-)-fluoxetine.
---
paper_title: Small Molecules as Chromatographic Tools for HPLC Enantiomeric Resolution: Pirkle-Type Chiral Stationary Phases Evolution

paper_content:

This review focuses on the evolution of Pirkle-type chiral stationary phases (CSPs), based on chiral recognition mechanism of small molecules and applications directly related with Medicinal Chemistry. Therefore, the strategies to plan these chiral selectors for enantioseparation of diverse therapeutic classes of chiral drugs and the understanding of the recognition mechanism are emphasized. The planning of Pirkle and co-workers to design different classes of CSPs was initially based on NMR studies, following the principle of reciprocity together with chromatographic results and studies of chiral recognition phenomena. All those features are described and critically discussed in this review. Finally, based on general principles established by Pirkle’s work it can be inferred that diverse chiral small molecules can be successfully used as chromatographic tools for enantiomeric resolution. In this context, several research groups were inspired on Pirkle’s design to develop new CSPs. Xanthone derivatives bonded to chiral groups were also exploited as selectors for CSPs and are briefly reported.
---
paper_title: Enantiomeric determination of azole antifungals in wastewater and sludge by liquid chromatography–tandem mass spectrometry

paper_content:

A sensitive and reliable liquid chromatographic-tandem mass spectrometric method for enantiomeric determination of five chiral azole antifungals (econazole, ketoconazole, miconazole, tebuconazole, and propiconazole) in wastewater and sludge has been established and validated. An isotope-labeled internal standard was used for quantification. Recovery of the individual enantiomers was usually in the range of 77-102 % for wastewater and 71-95 % for sludge, with relative standard deviations within 20 %. No significant difference (p>0.05) was observed between recovery of pairs of enantiomers of the chiral azole antifungals except for those of tebuconazole. Method quantification limits for individual enantiomers were 0.3-10 ng L(-1) and 3-29 ng g(-1) dry weight for wastewater and sludge, respectively. The method was used to investigate the enantiomeric composition of the azole pharmaceuticals in wastewater and sludge samples from a sewage treatment plant in China. Enantiomers of miconazole, ketoconazole, and econazole were widely detected. The results showed that the azole antifungals in wastewater and sludge were generally racemic or marginally non-racemic. The method is a useful tool for investigation of the enantiomeric occurrence, behavior, and fate of the chiral azole antifungals in the environment.
---
paper_title: Simultaneous enantiomeric determination of propranolol, metoprolol, pindolol, and atenolol in natural waters by HPLC on new polysaccharide-based stationary phase using a highly selective molecularly imprinted polymer extraction.

paper_content:

A simple high performance liquid chromatography method HPLC-UV for simultaneous enantiomeric determination of propranolol, metoprolol, pindolol, and atenolol in natural water samples was developed and validated, using a molecularly imprinted polymer solid-phase extraction. To achieve this purpose, Lux(®) Cellulose-1/Sepapak-1 (cellulose tris-(3,5-dymethylphenylcarbamate)) (Phenomenex, Madrid, Spain) chiral stationary phase was used in gradient elution and normal phase mode at ambient temperature. The gradient elution program optimized consisted of a progressive change of the mobile phase polarity from n-hex/EtOH/DEA 90/10/0.5 (v/v/v) to 60/40/0.5 (v/v/v) in 13 min, delivered at a flow rate of 1.3 ml/min and a sudden change of flow rate to 2.3 ml/min in 1 min. Critical steps in any molecularly imprinted polymer extraction protocol such as the flow rate to load the water sample in the cartridges and the breakthrough volume were optimized to obtain the higher extraction recoveries for all compounds. In optimal conditions (100 ml breakthrough volume loaded at 2.0 ml/min), extraction recoveries for the four pairs of β-blockers were near 100%. The MIP-SPE-HPLC-UV method developed demonstrates good linearity (R(2) ≥ 0.99), precision, selectivity, and sensitivity. Method limit detection was 3.0 µg/l for propranolol and pindolol enantiomers and 20.0 and 22.0 µg/l for metoprolol and atenolol enantiomers, respectively. The proposed methodology should be suitable for routine control of these emerging pollutants in natural waters for a better understanding of the environmental impact and fate.
---
paper_title: Functionalized Graphene as a Gatekeeper for Chiral Molecules: An Alternative Concept for Chiral Separation

paper_content:

Author(s): Hauser, AW; Mardirossian, N; Panetier, JA; Head-Gordon, M; Bell, AT; Schwerdtfeger, P | Abstract: We propose a new method of chiral separation using functionalized nanoporous graphene as an example. Computational simulations based on density functional theory show that the attachment of a suitable chiral "bouncer" molecule to the pore rim prevents the passage of the undesired enantiomer while letting its mirror image through. © 2014 WILEY-VCH Verlag GmbH a Co. KGaA, Weinheim.
---
paper_title: Enantioselective biodegradation of pharmaceuticals, alprenolol and propranolol, by an activated sludge inoculum.

paper_content:

Biodegradation of chiral pharmaceuticals in the environment can be enantioselective. Thus quantification of enantiomeric fractions during the biodegradation process is crucial for assessing the fate of chiral pollutants. This work presents the biodegradation of alprenolol and propranolol using an activated sludge inoculum, monitored by a validated enantioselective HPLC method with fluorescence detection. The enantioseparation was optimized using a vancomycin-based chiral stationary phase under polar ionic mode. The method was validated using a minimal salts medium inoculated with activated sludge as matrix. The method was selective and linear in the range of 10-800 ng/ml, with a R²>0.99. The accuracy ranged from 85.0 percent to 103 percent, the recovery ranged from 79.9 percent to 103 percent, and the precision measured by the relative standard deviation (RSD) was <7.18 percent for intra-batch and <5.39 percent for inter-batch assays. The limits of quantification and detection for all enantiomers were 10 ng/ml and 2.5 ng/ml, respectively. The method was successfully applied to follow the biodegradation of the target pharmaceuticals using an activated sludge inoculum during a fifteen days assay. The results indicated slightly higher biodegradation rates for the S-enantiomeric forms of both beta-blockers. The presence of another carbon source maintained the enantioselective degradation pattern while enhancing biodegradation extent up to fourteen percent.
---
paper_title: Simultaneous enantiomeric analysis of pharmacologically active compounds in environmental samples by chiral LC-MS/MS with a macrocyclic antibiotic stationary phase.

paper_content:

This paper presents a multi-residue method for direct enantioselective separation of chiral pharmacologically active compounds in environmental matrices. The method is based on chiral liquid chromatography and tandem mass spectrometry detection. Simultaneous chiral discrimination was achieved with a macrocyclic glycopeptide-based column with antibiotic teicoplanin as a chiral selector working under reverse phase mode. For the first time, enantioresolution was reported for metabolites of ibuprofen: carboxyibuprofen and 2-hydroxyibuprofen with this chiral stationary phase. Moreover, enantiomers of chloramphenicol, ibuprofen, ifosfamide, indoprofen, ketoprofen, naproxen and praziquantel were also resolved. The overall performance of the method was satisfactory in terms of linearity, precision, accuracy and limits of detection. The method was successfully applied for monitoring of pharmacologically active compounds at enantiomeric level in influent and effluent wastewater and in river water. In addition, the chiral recognition and analytical performance of the teicoplanin-based column was critically compared with that of the α1 -acid glycoprotein chiral stationary phase. Copyright © 2017 John Wiley & Sons, Ltd.
---
paper_title: Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

paper_content:

This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA.
---
paper_title: Concentrations, enantiomeric compositions, and sources of HCH, DDT and chlordane in soils from the Pearl River Delta, South China.

paper_content:

Concentrations, and enantiomeric compositions of HCH, DDT and chlordane in 74 soils of the Pearl River Delta, South China were investigated. The mean concentrations of HCHs and DDTs descended in the order: crop soils>paddy soils>natural soils. The concentrations (ng/g dw) of p,p'-DDE, p,p'-DDT, p,p'-DDD and o,p'-DDT in crop soils were 0.14-231, 0.07-315, <DL-96.7 and 0.06-73.8, respectively, while those of chlordane were generally below 0.78 for trans-chlordane (TC) and 0.75 for cis-chlordane (CC). Enantiomeric factors (EF value) were determined for o,p'-DDT, alpha-HCH, TC and CC. Both preferential depletions of (-) enantiomer and (+) enantiomer were observed for o,p'-DDT and alpha-HCH, indicated by EF values either <0.5 or >0.5. An EF value >0.5 generally suggested a preferential degradation of the (-) enantiomers of both TC and CC. The racemic alpha-HCH observed in the soils with higher HCH concentrations indicated that the transformation from gamma-HCH (e.g. lindane) to alpha-HCH may be an important process in the soils. The isomer ratios of p,p'-DDT/(DDE+DDD), o,p'-DDT/p,p'-DDT and enantiomeric compositions of o,p'-DDT suggested that both illegal use of technical DDT and the DDT impurity in dicofol may be responsible for the freshly DDT input in the region. The sources of DDTs were drawn by principal component analysis-multiple linear regression (PCA-MLR). The relative contributions of dicofol-type DDT, residues, and fresh technical DDT were estimated to be 55%, 21% and 17%, respectively. In addition, CC was found to degraded faster than TC in soils from the Pearl River Delta. The study demonstrated that the combination of isomer ratios and enantiomeric composition analysis may provide critical information on the potential sources and fate of organochlorine pesticides in soil.
---
paper_title: Enantiomer separation by enantioselective inclusion complexation–organic solvent nanofiltration

paper_content:

A novel chiral separation process, which utilizes a combination of enantioselective inclusion complexation (EIC) and organic solvent nanofiltration (OSN), was developed. Although EIC is an attractive way to resolve racemates, the difficulties associated with enantiomer recovery and chiral host recycle has limited large-scale applications. EIC coupled with OSN replaces distillation for the recovery of enantiomers from enantioenriched solid complex. A decomplexation solvent is employed to dissociate enantiomers from the complex, and subsequent separation of enantiomers from the chiral host is realized using OSN. The new process was investigated using racemic 1-phenylethanol as the guest and (R,R)-TADDOL as the chiral host. This novel technology expands the application of EIC to the resolution of nonvolatile racemates, and enables large-scale application.
---
paper_title: Enantiomeric profiling of a chemically diverse mixture of chiral pharmaceuticals in urban water.

paper_content:

Due to concerns regarding the release of pharmaceuticals into the environment and the understudied impact of stereochemistry of pharmaceuticals on their fate and biological potency, we focussed in this paper on stereoselective transformation pathways of selected chiral pharmaceuticals (16 pairs) at both microcosm (receiving waters and activated sludge wastewater treatment simulating microcosms) and macrocosm (wastewater treatment plant (WWTP) utilising activated sludge technology and receiving waters) scales in order to test the hypothesis that biodegradation of chiral drugs is stereoselective. Our monitoring programme of a full scale activated sludge WWTP and receiving environment revealed that several chiral drugs, those being marketed mostly as racemates, are present in wastewater and receiving waters enriched with one enantiomeric form (e.g. fluoxetine, mirtazapine, salbutamol, MDMA). This is most likely due to biological metabolic processes occurring in humans and other organisms. Both activated sludge and receiving waters simulating microcosms confirmed our hypothesis that chiral drugs are subject to stereoselective microbial degradation. It led, in this research, to preferential degradation of S-(+)-enantiomers of amphetamines, R-(+)-enantiomers of beta-blockers and S-(+)-enantiomers of antidepressants. In the case of three parent compound - metabolite pairs (venlafaxine - desmethylvenlafaxine, citalopram - desmethylcitalopram and MDMA - MDA), while parent compounds showed higher resistance to both microbial metabolism and photodegradation, their desmethyl metabolites showed much higher degradation rate both in terms of stereoselective metabolic and non-stereoselective photochemical processes. It is also worth noting that metabolites tend to be, as expected, enriched with enantiomers of opposite configuration to their parent compounds, which might have significant toxicological consequences when evaluating the metabolic residues of chiral pollutants.
---
paper_title: Enantioselective degradation of warfarin in soils

paper_content:

Environmental enantioselectivity information is important to fate assessment of chiral contaminants. Warfarin, a rodenticide and prescription medicine, is a chiral chemical but used in racemic form. Little is known about its enantioselective behavior in the environment. In this study, enantioselective degradation of warfarin in a turfgrass and a groundcover soils was examined in aerobic and ambient temperature conditions. An enantioselective analytical method was established using a novel triproline chiral stationary phase in high performance liquid chromatography. Unusual peak profile patterns, i.e., first peak (S(−)) broadening/second peak (R(+)) compression with hexane (0.1%TFA)/2-propanol (92/8, v/v) mobile phase, and first peak compression/second peak broadening with the (96/4, v/v) mobile phase, were observed in enantioseparation. This unique tunable peak property was leveraged in evaluating warfarin enantioselective degradation in two types of soil. Warfarin was extracted in high recovery from soil using methylene chloride after an aqueous phase basic-acidic conversion. No apparent degradation of warfarin was observed in the sterile turfgrass and groundcover soils during the 28 days incubation, while it showed quick degradation (half-life <7 days) in the nonsterile soils after a short lag period, suggesting warfarin degradation in the soils was mainly caused by micro-organisms. Limited enantioselectivity was found in the both soils, which was the R(+) enantiomer was preferentially degraded. The half-lives in turfgrass soil were 5.06 ± 0.13 and 5.97 ± 0.05 days, for the R(+) and the S(−) enantiomer, respectively. The corresponding values for the groundcover soil were 4.15 ± 0.11 and 4.47 ± 0.08 days. Chirality, 2011. © 2011 Wiley Periodicals, Inc.
---
paper_title: Enantioselective quantification of fluoxetine and norfluoxetine by HPLC in wastewater effluents.

paper_content:

Microbial degradation is the most important process to remove organic pollutants in Waste Water Treatment Plants. Regarding chiral compounds this process is normally enantioselective and needs the suitable analytical methodology to follow the removal of both enantiomers in an accurate way. Thus, this paper describes the development and validation of an enantioselective High Performance Liquid Chromatography with Fluorescence Detection (HPLC-FD) method for simultaneous analysis of fluoxetine (FLX) and norfluoxetine (NFLX) in wastewater effluents. Briefly, this method preconcentrated a small volume of wastewater samples (50 mL) on 500 mg Oasis MCX cartridges and used HPLC-FD with a vancomycin-based chiral stationary phase under reversed mode for analyses. The optimized mobile phase was EtOH/aqueous ammonium acetate buffer (92.5/7.5, v/v) at pH 6.8. The effect of EtOH percentage, buffer concentration, pH, column oven temperature and flow rate on chromatographic parameters was systematically investigated. The developed method was validated within the wastewater effluent used in microcosms laboratory assays. Linearity (R(2)>0.99), selectivity and sensitivity were achieved in the range of 4.0-60 ng mL(-1) for enantiomers of FLX and 2.0-30 ng mL(-1) for enantiomers of NFLX. The limits of detection were between 0.8 and 2.0 ng mL(-1) and the limits of quantification were between 2.0 and 4.0 ng mL(-1) for both enantiomers of FLX and the enantiomers of its demethylated metabolite NFLX. The validated method was successfully applied and proved to be robust to follow the degradation of both enantiomers of FLX in wastewater samples, during 46 days.
---
paper_title: Distinct Enantiomeric Signals of Ibuprofen and Naproxen in Treated Wastewater and Sewer Overflow

paper_content:

Ibuprofen and naproxen are commonly used members of a class of pharmaceuticals known as 2-arylpropionic acids (2-APAs). Both are chiral chemicals and can exist as either of two (R)- and (S)-enantiomers. Enantioselective analyses of effluents from municipal wastewater treatment plants (WWTPs) and from untreated sewage overflow reveal distinctly different enantiomeric fractions for both pharmaceuticals. The (S)-enantiomers of both were dominant in untreated sewage overflow, but the relative proportions of the (R)-enantiomers were shown to be increased in WWTP effluents. (R)-naproxen was below method detection limits (<1 ng.L(-1)) in sewage overflow, but measurable at higher concentrations in WWTP effluents. Accordingly, enantiomeric fractions (EF) for naproxen were consistently 1.0 in sewage overflow, but ranged from 0.7–0.9 in WWTP effluents. Ibuprofen EF ranged from 0.6–0.8 in sewage overflow and receiving waters, and was 0.5 in two WWTP effluents. Strong evidence is provided to indicate that chiral inversion of (S)-2-APAs to produce (R)-2-APAs may occur during wastewater treatment processes. It is concluded that this characterization of the enantiomeric fractions for ibuprofen and naproxen in particular effluents could facilitate the distinction of treated and untreated sources of pharmaceutical contamination in surface waters.
---
paper_title: Fate of pharmaceuticals in rivers : Deriving a benchmark dataset at favorable attenuation conditions

paper_content:

Abstract Pharmaceutical residues are commonly detected organic micropollutants in the aquatic environment. Their actual fate in rivers is still incompletely understood as their elimination is highly substance specific and studies often report contradictory results. To elucidate the ceiling of attenuation rates of pharmaceuticals in rivers we carried out a study at a river with favorable conditions for the elimination of organic micropollutants. Experiments were carried out at a small stream in Germany. Composite samples were taken at both ends of a 12.5 km long river stretch located downstream of a sewage treatment plant and analyzed for 10 pharmaceuticals. Moreover, pore water samples were taken and in situ photolysis experiments at several sites within the river stretch were performed to assess the importance of these individual elimination mechanisms. Pharmaceutical concentration in the surface water at the first sampling site ranged from 3.5 ng L−1 for propranolol to 1400 ng L−1 for diclofenac. In comparison to carbamazepine which was used as persistent tracer, all other pharmaceuticals were attenuated along the river stretch. Their elimination was higher in a sunny, dry weather period (period I) compared to a period with elevated discharge after a heavy rainfall (period II). Overall, the measured elimination rates ranged from 25% for sulfamethoxazole (period II) to 70% for propranolol (period I). Photolysis was only a relevant elimination process for diclofenac and potentially also for sotalol; for these compounds phototransformation half-life times of some hours were determined in the unshaded parts of the river. Biotransformation in the sediments was also an important attenuation process since the concentrations of the other pharmaceuticals in the sediments decreased relative to carbamazepine with depth. For the chiral betablocker metoprolol this biotransformation was also confirmed by a decrease in the enantiomer fractionation from 0.49 at site A to 0.43 at site B and to
---
paper_title: Characterization of pharmaceutically active compounds in Dongting Lake, China: Occurrence, chiral profiling and environmental risk.

paper_content:

Twenty commonly used pharmaceuticals including eight chiral drugs were investigated in Dongting Lake, China. The contamination level was relatively low on a global scale. Twelve pharmaceuticals were identified. The most abundant compound was caffeine followed by diclofenac, DEET, mefenamic acid, fluoxetine, ibuprofen and carbamazepine with mean concentrations from 2.0 to 80.8ngL(-1). Concentrations between East and West Dongting Lake showed spatial difference, with the West Dongting Lake less polluted. The relatively high ratio of caffeine versus carbamazepine (over 50) may indicate there was possible direct discharge of domestic wastewater into the lake. This is the first study presenting a survey allowing for comprehensive analysis of multiclass achiral and chiral pharmaceuticals including beta-blockers, antidepressants and anti-inflammatory drugs in freshwater lake. The enantiomeric compositions presented racemic to weakly enantioselective, with the highest enantiomeric fraction (EF) of 0.63 for fluoxetine. Meanwhile, venlafaxine was identified and evaluated the environment risk in surface water in China for the first time. The results of risk assessment suggested that fluoxetine, venlafaxine and diclofenac acid might pose a significant risk to aquatic organisms in Dongting Lake. The resulting data will be useful to enrich the research of emerging pollutants in freshwater lake and stereochemistry for environment investigations.
---
paper_title: Determination of the rotational barriers of atropisomeric polychlorinated biphenyls (PCBs) by a novel stopped-flow multidimensional gas chromatographic technique

paper_content:

The rotational barriers DG ‡ (T ) of the four atropisomeric polychlori- nated biphenyls (PCBs) 2,28,3,58,6-pentachlorobiphenyl (PCB 95), 2,283,38,4,68- hexachlorobiphenyl (PCB 132), 2,28,3,38,6,68-hexachlorobiphenyl (PCB 136), and 2,28,3,48,58,6-hexachlorobiphenyl (PCB 149) were determined via on-line enantiomeriza- tion kinetics by a new stopped-flow multidimensional gas chromatographic technique (stopped-flow MDGC) employing Chirasil-Dex as chiral stationary phase for enantiomer separation. The calculated rotational barriers DG ‡ (T ) of the trichloro-ortho-substituted atropisomers are 184 ± 2 kJ/mol for PCB 95, 189 ± 4 kJ/mol for PCB 132, and 184 ± 1 kJ/mol for PCB 149 at 300°C. The rotational barrier DG ‡ (T ) of tetrachloro-ortho- substituted PCB 136 is at least (or higher than) 210 kJ/mol at 320°C. Chirality 10:316- 320, 1998. © 1998 Wiley-Liss, Inc.
---
paper_title: Stereoisomer quantification of the β-blocker drugs atenolol, metoprolol, and propranolol in wastewaters by chiral high-performance liquid chromatography–tandem mass spectrometry

paper_content:

A chiral liquid chromatography–tandem mass spectrometry (HPLC-MS–MS) method was developed and validated for measuring individual enantiomers of three β-blocker drugs (atenolol, metoprolol, and propranolol) in wastewater treatment plant (WWTP) influents and effluents. Mean recoveries of the pharmaceuticals ranged from 67 to 106%, and the limits of detection of the analytes were 2–17 ng/L in wastewater effluents. The method was demonstrated by measuring, for the first time, the stereoisomer composition of target analytes in raw and treated wastewaters of two Canadian WWTPs. In these trials, racemic amounts of the three drugs were observed in influent of one wastewater treatment plant, but nonracemic amounts were observed in another. Effluents of the two plants contained nonracemic amounts of the drugs. These results indicate that biologically-mediated stereoselective processes that differ among WWTPs had occurred to eliminate individual enantiomers of the target analytes.
---
paper_title: Trace analysis of fluoxetine and its metabolite norfluoxetine. Part II : Enantioselective quantification and studies of matrix effects in raw and treated wastewater by solid phase extraction and liquid chromatography-tandem mass spectrometry

paper_content:

The isotope-labeled compounds fluoxetine-d5 and norfluoxetine-d5 were used to study matrix effects caused by co-eluting compounds originating from raw and treated wastewater samples, collected in U ...
---
paper_title: Occurrence and behavior of the chiral anti-inflammatory drug naproxen in an aquatic environment

paper_content:

The present study reports on the occurrence and chiral behavior of the anti-inflammatory drug (S)-naproxen (NAP)-(S)-2-(6-methoxynaphthalen-2-yl)propionic acid-in an aquatic environment under both field and laboratory conditions. In influents and effluents of sewage treatment plants (STPs) in the Tama River basin (Tokyo), (S)-NAP was detected at concentrations of 0.03 µg L(-1) to 0.43 µg L(-1) and 0.01 µg L(-1) to 0.11 µg L(-1), respectively. The concentrations of a major metabolite, 6-O-desmethyl NAP (DM-NAP) were up to 0.47 µg L(-1) and 0.56 µg L(-1) in influents and effluents, respectively. (R)-naproxen was not detected in STP influents, although it was present in effluents, and the enantiomeric faction (= S/[S + R]) of NAP ranged from 0.88 to 0.91. Under laboratory conditions with activated sludge from STPs, rapid degradation of (S)-NAP to DM-NAP and chiral inversion of (S)-NAP to (R)-NAP were observed. During river die-away experiments, degradation and chiral inversion of NAP were extremely slow. In addition, chiral inversion of (S)-NAP to (R)-NAP was not observed during photodegradation experiments. In the river receiving STP discharge, NAP and DM-NAP concentrations reached 0.08 µg L(-1) and 0.16 µg L(-1) , respectively. The enantiomeric faction of NAP in the river ranged from 0.84 to 0.98 and remained almost unchanged with the increasing contribution of rainfall to the river water. These results suggest that the absence and decrease of (R)-NAP in river waters could indicate the inflow of untreated sewage. E
---
paper_title: Simultaneous determination of chiral pesticide flufiprole enantiomers in vegetables, fruits, and soil by high-performance liquid chromatography

paper_content:

A simple and reliable method for the simultaneous determination of chiral pesticide flufiprole enantiomers using high-performance liquid chromatography has been established. The separation and determination were performed using reversed-phase chromatography on a carbamoyl–cellulose-type chiral stationary phase, a Lux Cellulose-2 column. The effects of different mobile phase composition on separation were discussed. The absolute configuration of flufiprole enantiomers was measured through the combination of experimental and predicted ECD spectra. An Alumina-N solid-phase extraction (SPE) column was used in the cleanup of the vegetables, fruits, and soil samples. The method was evaluated by the specificity, matrix effect, linearity, precision, accuracy and stability. The mean recoveries of two enantiomers ranged from 86.8 to 98.9 %, with 1.1–6.4 % intra-day relative standard deviation (RSD) and 1.2 to 5.8 % inter-day RSD. Good linearity (R 2 > 0.998) was obtained for all analyte matrix calibration curves within the range of 0.2–20 mg L−1. The limit of detection for two enantiomers in the six matrices was 0.007–0.008 mg kg−1, whereas the limit of quantification of two enantiomers in fruits, vegetables, and soil was 0.021–0.025 mg kg−1. The results confirmed that this method was convenient and accurate for the simultaneous determination of flufiprole enantiomers in food and environmental samples.
---
paper_title: Pharmaceutical and biomedical applications of enantioseparations using liquid chromatographic techniques.

paper_content:

The chiral separation methods using liquid chromatographic techniques can be divided into two categories: one is a direct method, which is based on a diastereomer formation on stationary phase or in mobile phase. The other is an indirect method, which is based on a diasteromer formation by reaction with a homochiral reagent. The enantiomer separation on a chiral stationary phases followed by derivatization with an achiral reagent is also dealt with this review article as the indirect method. The pharmaceutical and biomedical applications of enantioseparations using the direct and indirect methods have been considered in this review.
---
paper_title: A New Chiral Residue Analysis Method for Triazole Fungicides in Water Using Dispersive Liquid-Liquid Microextraction (DLLME)

paper_content:

A rapid, simple, reliable, and environment-friendly method for the residue analysis of the enantiomers of four chiral fungicides including hexaconazole, triadimefon, tebuconazole, and penconazole in water samples was developed by dispersive liquid-liquid microextraction (DLLME) pretreatment followed by chiral high-performance liquid chromatography (HPLC)-DAD detection. The enantiomers were separated on a Chiralpak IC column by HPLC applying n-hexane or petroleum ether as mobile phase and ethanol or isopropanol as modifier. The influences of mobile phase composition and temperature on the resolution were investigated and most of the enantiomers could be completely separated in 20 min under optimized conditions. The thermodynamic parameters indicated that the separation was enthalpy-driven. The elution orders were detected by both circular dichroism detector (CD) and optical rotatory dispersion detector (ORD). Parameters affecting the DLLME performance for pretreatment of the chiral fungicides residue in water samples, such as the extraction and dispersive solvents and their volume, were studied and optimized. Under the optimum microextraction condition the enrichment factors were over 121 and the linearities were 30-1500 µg L(-1) with the correlation coefficients (R(2)) over 0.9988 and the recoveries were between 88.7% and 103.7% at the spiking levels of 0.5, 0.25, and 0.05 mg L(-1) (for each enantiomer) with relative standard deviations varying from 1.38% to 6.70% (n = 6) The limits of detection (LODs) ranged from 8.5 to 29.0 µg L(-1) (S/N = 3).
---
paper_title: Enantiomeric Fraction Determination of 2-Arylpropionic Acids in a Package Plant Membrane Bioreactor

paper_content:

Enantiomeric compositions of three 2-arylpropionic acid (2-APA) drugs, ibuprofen, naproxen, and ketoprofen, were monitored in a membrane bioreactor (MBR) treating municipal effluent in a small rural town in Australia. Specific enantiomers were determined as amide diastereomers using the chiral derivatizing reagent, (R)-1-phenylethylamine (PEA), followed by gas chromatography-tandem mass spectrometry (GC-MS/MS). The six individual enantiomers were quantified by isotope dilution and the enantiomeric fractions (EFs) were determined. Over four separate sampling events, ibuprofen EF ranged from 0.88 to 0.94 (median 0.93) in the influent and 0.38 to 0.40 (median 0.39) in the effluent. However, no significant change in ketoprofen EF was observed, with influent EFs of 0.56-0.60 (median 0.58) and effluent EFs 0.54-0.68 (median 0.56). This is the first report of enantiospecific analysis of ketoprofen in municipal wastewater and it is not yet clear why such different behavior was observed compared to ibuprofen. Naproxen EF was consistently measured at 0.99 in the influent and ranged from 0.86 to 0.94 (median 0.91) in the effluent. This study demonstrates that EF is a relatively stable parameter and does not fluctuate according to concentration or other short-term variables introduced by sampling limitations. The enantiospecific analysis of chiral chemicals presents a promising approach to elucidate a more thorough understanding of biological treatment processes and a potential tool for monitoring the performance of key biological pathways.
---
paper_title: Strategy for Correction of Matrix Effect on the Determination of Pesticides in Water Bodies Using SPME-GC-FID

paper_content:

This paper investigates a strategy as a quality control parameter, using standard surrogate and determination of a relation factor for determination of parathion-methyl, chlorpyriphos and cypermethrin pesticides in environmental aqueous matrices with distinct characteristics (river water, estuarine, seawater and weir water), using the technique of solid phase microextraction gas chromatography with flame ionization detector (SPME-GC-FID). Pesticides were very susceptible to matrix effects promoted by environmental samples. The salinity and the organic matter seem to have been the main sources of interference in the method. For chlorpyriphos, in middle and high levels, the values of relation factor (Rf) for estuarines, seawater and weir matrices were statistically similar. For cypermethrin, the statistical equality occurred in estuarine matrices in medium and high levels of concentration. That indicates proportional behavior between the pesticide and the surrogate recovery, suggesting that a single value of Rf can be used as correction factor recovery for any of these matrices.
---
paper_title: Enantioseparation of chiral pharmaceuticals in biomedical and environmental analyses by liquid chromatography: An overview

paper_content:

Abstract This review aims to present the issues associated to enantioseparation of chiral pharmaceuticals in biological and environmental matrices using chiral stationary phases (CSP). Thus, it related some enantioselective methods in liquid chromatography (LC) and compares the importance given to chiral separation in biomedical and environmental fields. For that the most used CSP, the enantioselective chromatographic methods, their advantages and drawbacks were swiftly revised and compared. The recent advances and the limitations of chiral analytical methods in LC were also discussed.
---
paper_title: Recent progresses in protein-based chiral stationary phases for enantioseparations in liquid chromatography.

paper_content:

Chiral stationary phases (CSPs) based on proteins orglycoproteins have been developed for the enantioseparations of various compounds. In 2001, a review article [J. Haginaka, J. Chromatogr. A, 906 (2001) 253] dealing with CSPs based on proteins and glycoproteins was published. After that serum albumin from other species, penicillin G-acylase, antibodies, fatty acid binding protein and streptavidin were newly introduced as the chiral selectors in CSPs. This review article deals with recent progresses in CSPs based on protein or glycoproteins in LC after 2001, focusing on their enantioselective properties and chiral recognition mechanisms.
---
paper_title: Chiral stationary phase optimized selectivity liquid chromatography: A strategy for the separation of chiral isomers

paper_content:

Chiral Stationary-Phase Optimized Selectivity Liquid Chromatography (SOSLC) is proposed as a tool to optimally separate mixtures of enantiomers on a set of commercially available coupled chiral columns. This approach allows for the prediction of the separation profiles on any possible combination of the chiral stationary phases based on a limited number of preliminary analyses, followed by automated selection of the optimal column combination. Both the isocratic and gradient SOSLC approach were implemented for prediction of the retention times for a mixture of 4 chiral pairs on all possible combinations of the 5 commercial chiral columns. Predictions in isocratic and gradient mode were performed with a commercially available and with an in-house developed Microsoft visual basic algorithm, respectively. Optimal predictions in the isocratic mode required the coupling of 4 columns whereby relative deviations between the predicted and experimental retention times ranged between 2 and 7%. Gradient predictions led to the coupling of 3 chiral columns allowing baseline separation of all solutes, whereby differences between predictions and experiments ranged between 0 and 12%. The methodology is a novel tool allowing optimizing the separation of mixtures of optical isomers.
---
paper_title: Chiral analysis of organochlorine pesticides in Alabama soils.

paper_content:

The enantiomeric composition of organochlorine (OC) pesticide residues was investigated in 32 agricultural and 3 cemetery soils from Alabama. The enantiomeric signatures were similar to those from other soils in US and Canada. The enantiomer fractions (EFs) of o,p'-DDT showed great variability, ranging from 0.41 to 0.57 while the EFs of chlordanes and chlordane metabolites were less variable and differed in general significantly from racemic. Enantioselective depletion of (+)trans-chlordane, (-)cis-chlordane, the first eluting enantiomer of MC5, and enrichment of (+)heptachlor-exo-epoxide and (+)oxychlordane was found in a large majority of the samples with detectable residues. The enantiomeric composition of alpha-hexachlorocyclohexane was racemic or close to racemic.
---
paper_title: Recent advances in gas chromatography for solid and liquid stationary phases containing metal ions.

paper_content:

This review is devoted to the application of metal complexes as column packings and liquid stationary phases in gas chromatography. Particular attention is paid to the stationary phases with nitrogen-containing functional groups (e.g., amine and ketoimine) and beta-diketonates on the modified silica surface. The review also concerns the results of the research on metallomesogenes and chiral stationary phases. The factors influencing the retention mechanism in complexation gas chromatography are discussed. Practical application of the metal chelate-containing chromatographic packings for analytical separation of organic substances is considered.
---
paper_title: Loadings, trends, comparisons, and fate of achiral and chiral pharmaceuticals in wastewaters from urban tertiary and rural aerated lagoon treatments.

paper_content:

A comparison of time-weighted average pharmaceutical concentrations, loadings and enantiomer fractions (EFs) was made among treated wastewater from one rural aerated lagoon and from two urban tertiary wastewater treatment plants (WWTPs) in Alberta, Canada. Passive samplers were deployed directly in treated effluent for nearly continuous monitoring of temporal trends between July 2007 and April 2008. In aerated lagoon effluent, concentrations of some drugs changed over time, with some higher concentrations in winter likely due to reduced attenuation from lower temperatures (e.g., less microbially mediated biotransformation) and reduced photolysis from ice cover over lagoons; however, concentrations of some drugs (e.g. antibiotics) may also be influenced by changing use patterns over the year. Winter loadings to receiving waters for the sum of all drugs were 700 and 400 g/day from the two urban plants, compared with 4 g/day from the rural plant. Per capita loadings were similar amongst all plants. This result indicates that measured loadings, weighted by population served by WWTPs, are a good predictor of other effluent concentrations, even among different treatment types. Temporal changes in chiral drug EFs were observed in the effluent of aerated lagoons, and some differences in EF were found among WWTPs. This result suggests that there may be some variation of microbial biotransformation of drugs in WWTPs among plants and treatment types, and that the latter may be a good predictor of EF for some, but not all drugs.
---
paper_title: Enantioselective analysis of ibuprofen, ketoprofen and naproxen in wastewater and environmental water samples.

paper_content:

A highly sensitive and reliable method for the enantioselective analysis of ibuprofen, ketoprofen and naproxen in wastewater and environmental water samples has been developed. These three pharmaceuticals are chiral molecules and the variable presence of their individual (R)- and (S)-enantiomers is of increasing interest for environmental analysis. An indirect method for enantioseparation was achieved by the derivatization of the (R)- and (S)-enantiomers to amide diastereomers using (R)-1-phenylethylamine ((R)-1-PEA). After initial solid phase extraction from aqueous samples, derivatization was undertaken at room temperature in less than 5 min. Optimum recovery and clean-up of the amide diastereomers from the derivatization solution was achieved by a second solid phase extraction step. Separation and detection of the individual diastereomers was undertaken by gas chromatography-tandem mass spectrometry (GC-MS/MS). Excellent analyte separation and peak shapes were achieved for the derivatized (R)- and (S)-enantiomers for all three pharmaceuticals with peak resolution, R(s) is in the range of 2.87-4.02 for all diastereomer pairs. Furthermore, the calibration curves developed for the (S)-enantiomers revealed excellent linearity (r(2) ≥ 0.99) for all three compounds. Method detection limits were shown to be within the range of 0.2-3.3 ng L(-1) for individual enantiomers in ultrapure water, drinking water, surface water and a synthetic wastewater. Finally, the method was shown to perform well on a real tertiary treated wastewater sample, revealing measurable concentrations of both (R)- and (S)-enantiomers of ibuprofen, naproxen and ketoprofen. Isotope dilution using racemic D(3)-ibuprofen, racemic D(3)-ketoprofen and racemic D(3)-naproxen was shown to be an essential aspect of this method for accurate quantification and enantiomeric fraction (EF) determination. This approach produced excellent reproducibility for EF determination of triplicate tertiary treated wastewater samples.
---
paper_title: Enantiomeric fraction evaluation of pharmaceuticals in environmental matrices by liquid chromatography-tandem mass spectrometry

paper_content:

Abstract The interest for environmental fate assessment of chiral pharmaceuticals is increasing and enantioselective analytical methods are mandatory. This study presents an enantioselective analytical method for the quantification of seven pairs of enantiomers of pharmaceuticals and a pair of a metabolite. The selected chiral pharmaceuticals belong to three different therapeutic classes, namely selective serotonin reuptake inhibitors (venlafaxine, fluoxetine and its metabolite norfluoxetine), beta-blockers (alprenolol, bisoprolol, metoprolol, propranolol) and a beta 2 -adrenergic agonist (salbutamol). The analytical method was based on solid phase extraction followed by liquid chromatography tandem mass spectrometry with a triple quadrupole analyser. Briefly, Oasis® MCX cartridges were used to preconcentrate 250 mL of water samples and the reconstituted extracts were analysed with a Chirobiotic™ V under reversed mode. The effluent of a laboratory-scale aerobic granular sludge sequencing batch reactor (AGS-SBR) was used to validate the method. Linearity ( r 2 > 0.99), selectivity and sensitivity were achieved in the range of 20–400 ng L −1 for all enantiomers, except for norfluoxetine enantiomers which range covered 30–400 ng L −1 . The method detection limits were between 0.65 and 11.5 ng L −1 and the method quantification limits were between 1.98 and 19.7 ng L −1 . The identity of all enantiomers was confirmed using two MS/MS transitions and its ion ratios, according to European Commission Decision 2002/657/EC. This method was successfully applied to evaluate effluents of wastewater treatment plants (WWTP) in Portugal. Venlafaxine and fluoxetine were quantified as non-racemic mixtures (enantiomeric fraction ≠ 0.5). The enantioselective validated method was able to monitor chiral pharmaceuticals in WWTP effluents and has potential to assess the enantioselective biodegradation in bioreactors. Further application in environmental matrices as surface and estuarine waters can be exploited.
---
paper_title: Spatial and temporal occurrence of pharmaceuticals and illicit drugs in the aqueous environment and during wastewater treatment: new developments.

paper_content:

This paper presents, for the first time, spatial and temporal occurrence of a comprehensive set of >60 pharmaceuticals, illicit drugs and their metabolites in wastewater (7 wastewater treatment plants utilising different treatment technologies) and a major river in the UK over a 12 month period. This paper also undertakes a comparison of the efficiency of processes utilised during wastewater treatment and it discusses under-researched aspects of pharmaceuticals and illicit drugs in the environment including sorption to solids and stereoselectivity in the fate of chiral drugs during wastewater treatment and in receiving waters. The removal efficiency of analytes strongly depended on the type of wastewater treatment technology employed and denoted <50% or >60% in the case of tricking filter and activated sludge respectively. It should be stressed, however, that the removal rate was highly variable for different groups of compounds. A clear increase in the cumulative concentration of all monitored compounds was observed in receiving waters; thus highlighting the impact of WWTP discharge on water quality and the importance of the removal efficiency of WWTPs. No seasonal variation was observed with regard to the total load of targeted compounds in the river each month. The concentration of each analyte was largely dependent on rainfall and the dilution factor of WWTP discharge. These results indicate that although the drugs of abuse are not present at very high concentrations in river water (typically low ng L(-1) levels), their occurrence and possible synergic action is of concern, and the study of multiple groups of drugs of abuse is of significant importance.
---
paper_title: Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms

paper_content:

Here presented for the first time is the enantioselective biodegradation of amphetamine and methamphetamine in river microcosm bioreactors. The aim of this investigation was to test the hypothesis that mechanisms governing the fate of amphetamine and methamphetamine in the environment are mostly stereoselective and biological in nature. Several bioreactors were studied over the duration of 15 days (i) in both biotic and abiotic conditions, (ii) in the dark or exposed to light and (iii) in the presence or absence of suspended particulate matter. Bioreactor samples were analysed using SPE-chiral-LC-(QTOF)MS methodology. This investigation has elucidated the fundamental mechanism for degradation of amphetamine and methamphetamine as being predominantly biological in origin. Furthermore, stereoselectivity and changes in enantiomeric fraction (EF) were only observed under biotic conditions. Neither amphetamine nor methamphetamine appeared to demonstrate adsorption to suspended particulate matter. Our experiments also demonstrated that amphetamine and methamphetamine were photo-stable. Illicit drugs are present in the environment at low concentrations but due to their pseudo-persistence and non-racemic behaviour, with two enantiomers revealing significantly different potency (and potentially different toxicity towards aquatic organisms) the risk posed by illicit drugs in the environment should not be under- or over-estimated. The above results demonstrate the need for re-evaluation of the procedures utilised in environmental risk assessment, which currently do not recognise the importance of the phenomenon of chirality in pharmacologically active compounds.
---
paper_title: A column-switching method for quantification of the enantiomers of omeprazole in native matrices of waste and estuarine water samples.

paper_content:

Abstract This work reports the use of a two-dimensional liquid chromatography (2D-LC) system for quantification of the enantiomers of omeprazole in distinct native aqueous matrices. An octyl restricted-access media bovine serum albumin column (RAM-BSA C8) was used in the first dimension, while a polysaccharide-based chiral column was used in the second dimension with either ultraviolet (UV–vis) or ion-trap tandem mass spectrometry (IT-MS/MS) detection. An in-line configuration was employed to assess the exclusion capacity of the RAM-BSA columns to humic substances. The excluded macromolecules had a molecular mass in the order of 18 kDa. Good selectivity, extraction efficiency, accuracy, and precision were achieved employing a very small amount (500 μL or 1.00 mL) of native water sample per injection, with detection limits of 5.00 μg L−1, using UV–vis, and 0.0250 μg L−1, using IT-MS/MS. The total analysis time was only 35 min, with no time spent on sample preparation. The methods were successfully applied to analyze a series of waste and estuarine water samples. The enantiomers were detected in an estuarine water sample collected from the Douro River estuary (Portugal) and in an influent sample from the wastewater treatment plant (WWTP) of Sao Carlos (Brazil). As far as we are concerned, this is the first report of the occurrence of (+)-omeprazole and (−)-omeprazole in native aqueous matrices.
---
paper_title: Enantiomeric analysis of drugs of abuse in wastewater by chiral liquid chromatography coupled with tandem mass spectrometry.

paper_content:

The manuscript concerns the development and validation of a method for enantiomeric analysis of structurally related amphetamines (amphetamine, methamphetamine, 4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)), ephedrines (ephedrine, pseudoephedrine and norephedrine) and venlafaxine in wastewater by means of chiral chromatography coupled with tandem mass spectrometry. Solid-phase extraction on Oasis HLB sorbent used for sample clean-up and concentration of analytes resulted in very good recoveries accounting for >70%. Signal suppression during MS analysis was negligible for most studied analytes. Resolution of enantiomers of chiral drugs was found to be higher than 1. Preliminary assay validation was undertaken. The mean correlation coefficients of the calibration curves, which were on average higher than 0.997 for all studied analytes, showed good linearity of the method in the studied range. Intra- and inter-day repeatabilities were on average less than 5%. The method quantification limits in wastewater were at low ppt levels and varied from 2.25 to 11.75ng/L. The method was successfully applied for the analysis of raw and treated wastewater samples collected from four wastewater treatment plants. A common occurrence of 1R,2S (-)-ephedrine, 1S,2S (+)-pseudoephedrine and venlafaxine in both raw and treated wastewater samples was observed. Amphetamine, methamphetamine, MDMA and MDEA were also detected in several wastewater samples. The study of enantiomeric fractions of these chiral drugs proved their variable non-racemic composition. The influence of wastewater treatment processes on the enantiomeric composition of chiral drugs was also noted and might indicate enantioselective processes occurring during treatment, although more comprehensive research has to be undertaken to support this hypothesis.
---
paper_title: Occurrence and Environmental Behavior of the Chiral Pharmaceutical Drug Ibuprofen in Surface Waters and in Wastewater

paper_content:

Pharmaceutical compounds can reach detectable concentrations in rivers and lakes if production and use are sufficiently large and the compounds show some mobility and persistence in the aquatic environment. In this study, we report on the occurrence and on the enantiomer composition of the chiral pharmaceutical drug ibuprofen (IB) in surface waters and in samples from wastewater treatment plants (WWTPs). Enantioselective gas chroma tography and detection by mass spectrometry/mass spectrometry was used for analysis. IB was present in influents of WWTPs at concentrations of up to 3 μg/L with a high enantiomeric excess of the pharmacologically active S enantiomer (S ≫ R), as from human urinary excretion. The principal human urinary metabolites of IB, hydroxy-IB and carboxy-IB, were observed in WWTP influents at even higher concentrations. In contrast to other pharmaceutical compounds such as clofibric acid and diclofenac, IB and its metabolites are then efficiently degraded (>95%) during treatment in WWTPs. ...
---
paper_title: Direct injection of native aqueous matrices by achiral–chiral chromatography ion trap mass spectrometry for simultaneous quantification of pantoprazole and lansoprazole enantiomers fractions

paper_content:

Abstract A two-dimensional liquid chromatography system coupled to ion-trap tandem mass spectrometer (2DLC-IT–MS/MS) was employed for the simultaneous quantification of pantoprazole and lansoprazole enantiomers fractions. A restricted access media of bovine serum albumin octyl column (RAM-BSA C 8 ) was used in the first dimension for the exclusion of the humic substances, while a polysaccharide-based chiral column was used in the second dimension for the enantioseparation of both pharmaceuticals. The results described here show good selectivity, extraction efficiency, accuracy, and precision with detection limits of 0.200 and 0.150 μg L −1 for the enatiomers of pantoprazole and lansoprazole respectively, while employing a small amount (1.0 mL) of native water sample per injection. This work reports an innovative assay for monitoring work, studies of biotic and abiotic enantioselective degradation and temporal changes of enantiomeric fractions.
---
paper_title: Enantioselective chromatography in drug discovery

paper_content:

Molecular chirality is a fundamental consideration in drug discovery, one necessary to understand and describe biological targets as well as to design effective pharmaceutical agents. Enantioselective chromatography has played an increasing role not only as an analytical tool for chiral analyses, but also as a preparative technique to obtain pure enantiomers from racemates quickly from a wide diversity of chemical structures. Different enantioselective chromatography techniques are reviewed here, with particular emphasis on the most widespread high performance liquid chromatography (HPLC) and the rapidly emerging supercritical fluid chromatography (SFC) techniques. This review focuses on the dramatic advances in the chiral stationary phases (CSPs) that have made HPLC and SFC indispensable techniques for drug discovery today. In addition, screening strategies for rapid method development and considerations for laboratory-scale preparative separation are discussed and recent achievements are highlighted.
---
paper_title: Multi-residue enantiomeric analysis of human and veterinary pharmaceuticals and their metabolites in environmental samples by chiral liquid chromatography coupled with tandem mass spectrometry detection

paper_content:

Enantiomeric profiling of chiral pharmacologically active compounds (PACs) in the environment has hardly been investigated. This manuscript describes, for the first time, a multi-residue enantioselective method for the analysis of human and veterinary chiral PACs and their main metabolites from different therapeutic groups in complex environmental samples such as wastewater and river water. Several analytes targeted in this paper have not been analysed in the environment at enantiomeric level before. These are aminorex, carboxyibuprofen, carprofen, cephalexin, 3-N-dechloroethylifosfamide, 10,11-dihydro-10-hydroxycarbamazepine, dihydroketoprofen, fenoprofen, fexofenadine, flurbiprofen, 2-hydroxyibuprofen, ifosfamide, indoprofen, mandelic acid, 2-phenylpropionic acid, praziquantel and tetramisole. The method is based on chiral liquid chromatography utilising a chiral α1-acid glycoprotein column and tandem mass spectrometry detection. Excellent chromatographic separation of enantiomers (Rs≥1.0) was achieved for chloramphenicol, fexofenadine, ifosfamide, naproxen, tetramisole, ibuprofen and their metabolites: aminorex and dihydroketoprofen (three of four enantiomers), and partial separation (Rs = 0.7-1.0) was achieved for ketoprofen, praziquantel and the following metabolites: 3-N-dechloroethylifosfamide and 10,11-dihydro-10-hydroxycarbamazepine. The overall performance of the method was satisfactory for most of the compounds targeted. Method detection limits were at low nanogram per litre for surface water and effluent wastewater. Method intra-day precision was on average under 20% and sample pre-concentration using solid phase extraction yielded recoveries >70% for most of the analytes. This novel, selective and sensitive method has been applied for the quantification of chiral PACs in surface water and effluent wastewater providing excellent enantioresolution of multicomponent mixtures in complex environmental samples. It will help with better understanding of the role of individual enantiomers in the environment and will enable more accurate environmental risk assessment.
---
paper_title: Trace analysis of fluoxetine and its metabolite norfluoxetine. Part I: development of a chiral liquid chromatography-tandem mass spectrometry method for wastewater samples.

paper_content:

An enantioselective method for the determination of fluoxetine (a selective serotonin reuptake inhibitor) and its pharmacologically active metabolite norfluoxetine has been developed for raw and tr ...
---
paper_title: Stopped-flow multidimensional gas chromatography: A new method for the determination of enantiomerization barriers

paper_content:

With the stopped-flow multidimensional gas chromatographic technique enantiomerization barriers of ΔG#(T)=70–200 kJ/mol can easily be determined. First, the racemic mixture is separated by gas chromatography on a chiral stationary phase, then one enantiomer is transferred into a heated empty reactor column where enantiomerization is performed on-line in an achiral environment in the gas phase, and finally the enantiomerized fraction is separated in a second chiral column. The enantiomerization barrier ΔG (T) can be calculated from the enantiomerization time, the observed enantiomeric ratio, and the enantiomerization temperature. Moreover, by calculating ΔG#(T) at different temperatures, ΔH# and ΔS# are accessible. With this method atropisomeric polychlorinated biphenyls, a chiral allene, and a chiral aziridine were investigated. ©1999 John Wiley & Sons, Inc. J Micro Sep 11: 475–479, 1999
---
paper_title: Chiral pharmaceuticals: A review on their environmental occurrence and fate processes

paper_content:

More than 50% of pharmaceuticals in current use are chiral compounds. Enantiomers of the same pharmaceutical have identical physicochemical properties, but may exhibit differences in pharmacokinetics, pharmacodynamics and toxicity. The advancement in separation and detection methods has made it possible to analyze trace amounts of chiral compounds in environmental media. As a result, interest on chiral analysis and evaluation of stereoselectivity in environmental occurrence, phase distribution and degradation of chiral pharmaceuticals has grown substantially in recent years. Here we review recent studies on the analysis, occurrence, and fate of chiral pharmaceuticals in engineered and natural environments. Monitoring studies have shown ubiquitous presence of chiral pharmaceuticals in wastewater, surface waters, sediments, and sludge, particularly β-receptor antagonists, analgesics, antifungals, and antidepressants. Selective sorption and microbial degradation have been demonstrated to result in enrichment of one enantiomer over the other. The changes in enantiomer composition may also be caused by biologically catalyzed chiral inversion. However, accurate evaluation of chiral pharmaceuticals as trace environmental pollutants is often hampered by the lack of identification of the stereoconfiguration of enantiomers. Furthermore, a systematic approach including occurrence, fate and transport in various environmental matrices is needed to minimize uncertainties in risk assessment of chiral pharmaceuticals as emerging environmental contaminants.
---
paper_title: Chiral signature of venlafaxine as a marker of biological attenuation processes.

paper_content:

The chiral signature of the antidepressant venlafaxine was used in this study to gain insight into biological attenuation processes and to differentiate abiotic and biotic transformation processes in water. Laboratory scale experiments revealed that sorption and phototransformation processes were not enantioselective while venlafaxine was enantioselectively biotransformed into O-desmethylvenlafaxine. The enantiomeric fraction (EF) variations of venlafaxine appeared to be proportional to its microbial fractional conversion. Enantioselective biotransformation of venlafaxine was also investigated in a eutrophic French river. Venlafaxine was found to be racemic at the output of the main wastewater treatment plant discharging into the river, independently of the sampling date during the year. An analysis of EF variations might provide evidence of biodegradation along a 30 km river stretch.
---
paper_title: Enantiomeric fractionation as a tool for quantitative assessment of biodegradation: The case of metoprolol.

paper_content:

An efficient chiral liquid chromatography high resolution mass spectrometry method has been developed for the determination of metoprolol (MTP) and three of its major metabolites, namely O-desmethylmetoprolol (O-DMTP), α-hydroxymetoprolol (α-HMTP) and metoprolol acid (MTPA) in wastewater treatment plant (WWTP) influents and effluents. The optimized analytical method has been validated with good quality parameters including resolution >1.3 and method quantification limits down to the ng/L range except for MTPA. On the basis of this newly developed analytical method, the stereochemistry of MTP and its metabolites was studied over time in effluent/sediment biotic and sterile microcosms under dark and light conditions and in influents and effluents of 5 different WWTPs. MTP stereoselective degradation was exclusively observed under biotic conditions, confirming the specificity of enantiomeric fraction variations to biodegradation processes. MTP was always biotransformed into MTPA with a (S)-enantiomer enrichment. The results of enantiomeric enrichment pointed the way for a quantitative assessment of in situ biodegradation processes due to a good fit (R(2) > 0.98) of the aerobic MTP biodegradation to the Rayleigh dependency in all the biotic microcosms and in WWTPs because both MTP enantiomers followed the same biodegradation kinetic profiles. These results demonstrate that enantiomeric fractionation constitutes a very interesting quantitative indicator of MTP biodegradation in WWTPs and probably in the environment.
---
paper_title: Enantioselective stopped-flow multidimensional gas chromatography. Determination of the inversion barrier of 1-chloro-2,2-dimethylaziridine.

paper_content:

Enantioselective stopped-flow multidimensional gas chromatography (stopped-flow MDGC) is a fast and simple technique to determine enantiomerization (inversion) barriers in the gas phase in a range of delta G#gas(T)=70-200 kJ mol(-1). After complete gas-chromatographic separation of the enantiomers in the first column, gas phase enantiomerization of the heart-cut fraction of one single enantiomer is performed in the second (reactor) column at increased temperature and afterwards this fraction is separated into the enantiomers in the third column. From the observed de novo enantiomeric peak areas a(j), the enantiomerization time t and the enantiomerization temperature T, the enantiomerization (inversion) barrier delta G#gas(T) is determined and from temperature-dependent experiments, the activation enthalpy delta H#gas and the activation entropy delta S#gas are obtained. Enantiomerization studies on chiral 1-chloro-2,2-dimethylaziridine by stopped-flow MDGC yielded activation parameters of nitrogen inversion in the gas phase, i.e., delta G#gas(353 K)=110.5+/-0.5 kJ mol(-1), delta H#gas=71.0+/-3.8 kJ mol(-1) and delta S#gas=-109+/-11 J mol(-1) K(-1). By the complementary method of dynamic gas chromatography (GC), the apparent enantiomerization (inversion) barrier of 1-chloro-2,2-dimethylaziridine in the gas-liquid biphase system was found delta G#app(353 K)=108 kJ mol(-1). The values obtained by stopped-flow MDGC in the gas phase were used to calculate the activation parameters of nitrogen inversion of 1-chloro-2,2-dimethylaziridine in the liquid phase in the presence of the chiral selector Chirasil-nickel(II), i.e.. deltaG#liq(353 K)=106.0+/-0.4 kJ mol(-1), delta H#liq=68.3+/-1.4 kJ mol(-1) and deltaS#liq=-106+/-3.0 J mol(-1) K(-1).
---
paper_title: Stereoisomer analysis of wastewater-derived β-blockers, selective serotonin re-uptake inhibitors, and salbutamol by high-performance liquid chromatography–tandem mass spectrometry

paper_content:

Abstract A reversed-phase enantioselective liquid chromatography–tandem mass spectrometry (HPLC-MS-MS) method was developed to measure enantiomer fractions (EF) and concentrations of pharmaceuticals in wastewater. Enantiomer resolution of six β-blockers (atenolol, metoprolol, nadolol, pindolol, propranolol, and sotalol) along with two selective serotonin re-uptake inhibitors (citalopram, fluoxetine) and one β 2 -agonist (salbutamol) was achieved with the Chirobiotic V stationary phase. Analyte recovery averaged 86% in influent and 78% in effluent with limits of detection ranging from 0.2 to 7.5 ng/L. These results represent an improvement in wastewater EF measurement for atenolol, metoprolol and propranolol as well as the first EF measurements of citalopram, fluoxetine, nadolol, pindolol, salbutamol and sotalol in wastewaters. Changes in EF through treatment indicate biologically mediated stereoselective processes were likely occurring during wastewater treatment.
---
paper_title: Source discrimination of drug residues in wastewater: The case of salbutamol.

paper_content:

Abstract Analytical methods used for pharmaceuticals and drugs of abuse in sewage play a fundamental role in wastewater-based epidemiology (WBE) studies. Here quantitative analysis of drug metabolites in raw wastewaters is used to determine consumption from general population. Its great advantage in public health studies is that it gives objective, real-time data about community use of chemicals, highlighting the relationship between environmental and human health. Within a WBE study on salbutamol use in a large population, we developed a procedure to distinguish human metabolic excretion from external source of contamination, possibly industrial, in wastewaters. Salbutamol is mainly excreted as the sulphate metabolite, which is rapidly hydrolyzed to the parent compound in the environment, so this is currently not detected. When a molecule is either excreted un-metabolized or its metabolites are unstable in the environment, studies can be completed by monitoring the parent compound. In this case it is mandatory to assess whether the drug in wastewater is present because of population use or because of a specific source of contamination, such as industrial manufacturing waste. Because commercial salbutamol mainly occurs as a racemic mixture and is stereoselective in the human metabolism, the enantiomeric relative fraction (EFrel) in wastewater samples should reflect excretion, being unbalanced towards one of two enantiomers, if the drug is of metabolic origin. The procedure described involves chiral analysis of the salbutamol enantiomers by liquid chromatography-tandem mass spectrometry (LC–MS-MS) and calculation of EFrel, to detect samples where external contamination occurs. Samples were collected daily between October and December 2013 from the Milano Nosedo wastewater treatment plant. Carbamazepine and atenolol were measured in the sewage collector, as “control” drugs. Salbutamol EFrel was highly consistent in all samples during this three-month period, but a limited number of samples had unexpectedly high concentrations where the EFrel was close to that observed of the un-metabolized, commercially available drug, supporting the idea of an external source of contamination, besides human metabolic excretion. Results showed that, when present, non-metabolic daily loads could be evaluated indicating an average of 4.12 g/day of salbutamol extra load due to non-metabolic sources. The stereoselectivity in metabolism and enantiomeric ratio analysis appears to be a useful approach in WBE studies to identify different sources of drugs in the environment, when no metabolic products are present at useful analytical levels.
---
paper_title: Determination of chiral pharmaceuticals and illicit drugs in wastewater and sludge using microwave assisted extraction, solid-phase extraction and chiral liquid chromatography coupled with tandem mass spectrometry.

paper_content:

This is the first study presenting a multi-residue method allowing for comprehensive analysis of several chiral pharmacologically active compounds (cPACs) including beta-blockers, antidepressants and amphetamines in wastewater and digested sludge at the enantiomeric level. Analysis of both the liquid and solid matrices within wastewater treatment is crucial to being able to carry out mass balance within these systems. The method developed comprises filtration, microwave assisted extraction and solid phase extraction followed by chiral liquid chromatography coupled with tandem mass spectrometry to analyse the enantiomers of 18 compounds within all three matrices. The method was successfully validated for 10 compounds within all three matrices (amphetamine, methamphetamine, MDMA, MDA, venlafaxine, desmethylvenlafaxine, citalopram, metoprolol, propranolol and sotalol), 7 compounds validated for the liquid matrices only (mirtazapine, salbutamol, fluoxetine, desmethylcitalopram, atenolol, ephedrine and pseudoephedrine) and 1 compound (alprenolol) passing the criteria for solid samples only. The method was then applied to wastewater samples; cPACs were found at concentration ranges in liquid matrices of: 1.7ngL(-1) (metoprolol) - 1321ngL(-1) (tramadol) in influent, Language: en
---
paper_title: Estimation of community-wide drugs use via stereoselective profiling of sewage

paper_content:

This paper explores possibilities of applying enantiomeric profiling to solving problems related to estimation of drugs usage in communities via the sewage epidemiology approach: for the identification of whether drug residue results from consumption of illicit drug or metabolism of other drugs, verification of potency of used drugs and monitoring of changing patterns of drugs abuse. Due to the very complex nature of wastewater used in sewage epidemiology, which comes from the whole community rather than one individual, verification of the above is challenging but vital in accurate estimations of drugs abuse as well as providing comprehensive information regarding drug abuse trends. The results of this study indicated that amphetamine in raw wastewater was enriched with R(-)-enantiomer due to its abuse as racemate. Methamphetamine was found to be racemic or to be enriched with S(+)-enantiomer. MDMA was enriched with R(-)-MDMA, which was to be expected as MDMA is abused as racemate. MDA was enriched with S(+)-enantiomer, which suggests that its presence might be associated with MDMA abuse and not intentional MDA use. Out of the four possible isomers of ephedrine only natural 1R,2S(-)-ephedrine and 1S,2S(+)-pseudoephedrine were detected in raw wastewater and their diastereomeric fractions were found to be season dependent with higher contribution from 1S,2S(+)-pseudoephedrine over winter months and an enrichment with 1R,2S(-)-ephedrine during the spring and summer months. These findings were accompanied by a decrease of cumulative concentration of ephedrines throughout the sampling campaign between February and August. This is a very important finding indicating that non-enantioselective measurement of ephedrine concentrations cannot be a reliable indicator of actual potency of ephedrines used.
---
paper_title: Chiral analysis of metoprolol and two of its metabolites, α-hydroxymetoprolol and deaminated metoprolol, in wastewater using liquid chromatography–tandem mass spectrometry

paper_content:

A LC–MS/MS method for the chiral separation of metoprolol and two of its main metabolites, α-hydroxymetoprolol (α-OH-Met) and deaminated metoprolol (COOH-Met), in environmental water samples has be ...
---
paper_title: Enantioselective and nonenantioselective degradation of organic pollutants in the marine ecosystem

paper_content:

Enantiomeric ratios of 11 chiral environmental pollutants determined in different compartments of the marine ecosystem by chiral capillary gas chromatography and chiral high-performance liquid chromatography allow discrimination between the following processes: enantioselective decomposition of both enantiomers with different velocities by marine microorganisms (α-HCH, β-PCCH, γ-PCCH); enantioselective decomposition of one enantiomer only by marine microorganisms (DCPP); enantioselective decomposition by enzymatic processes in marine biota (α-HCH, β-PCCH, trans-chlordane, cis-chlordane, octachlordane MC4, octachlordane MC5, octachlordane MC7, oxychlordane, heptachlor epoxide); enantioselective active transport through the “blood–brain barrier” (α-HCH); nonenantioselective photochemical degradation (α-HCH, β-PCCH). © 1993 Wiley-Liss, Inc.
---
paper_title: Enantiomers of α-Hexachlorocyclohexane as Tracers of Air−Water Gas Exchange in Lake Ontario

paper_content:

The technique of chiral phase capillary gas chromatography was applied to investigate the degradation and transport of the persistent chiral pesticide α-hexachlorocyclohexane (α-HCH) in the Lake Ontario environment. Chiral analysis gave the enantiomeric ratios (ERs) of α-HCH in samples taken May−October 1993 from the lake and its atmosphere. ERs of (+)α-HCH/(−)α-HCH for Lake Ontario surface and deep water samples were similar and averaged 0.85 ± 0.02 as compared with a value of 1.00 for the α-HCH standard. Higher ERs were observed in water samples from the Niagara River (0.91 ± 0.02) and from precipitation (1.00 ± 0.01). Air samples of α-HCH measured at 10 m above the lake show a seasonal variability with values near 1.00 in spring and fall and minimum values in individual samples near 0.90 in summer. A simple air−water gas transfer model demonstrates that enantiomeric ratios <1.0 in air are derived from equilibration of the air with the water during transport of the air mass over the lake. Based on the m...
---
paper_title: Variations in α-Hexachlorocyclohexane enantiomer ratios in relation to microbial activity in a temperate estuary

paper_content:

Changes in the enantiomer ratios (ERs) of chiral pollutants in the environment are often considered evidence of biological alteration despite the lack of data on causal or mechanistic relationships between microbial parameters and ER values. Enantiomer ratios that deviate from 1:1 in the environment provide evidence for the preferential microbial degradation of one enantiomer, whereas ER values equal to 1 provide no evidence for microbial degradation and may mistakenly be interpreted as evidence that biodegradation is not important. In an attempt to link biological and geochemical information related to enantioselective processes, we measured the ERs of the chiral pesticide α-hexachlorocyclohexane (α-HCH) and bacterial activity (normalized to abundance) in surface waters of the York River (VA, USA) bimonthly throughout one year. Despite lower overall α-HCH concentrations, α-HCH ER values were unexpectedly close to 1:1 in the freshwater region of the estuary with the highest bacterial activity. In contrast, ER values were nonracemic (ER ≠ 1) and α-HCH concentrations were significantly higher in the higher salinity region of the estuary, where bacterial activity was lower. Examination of these data may indicate that racemic environmental ER values are not necessarily reflective of a lack of biodegradation or recent input into the environment, and that nonenantioselective biodegradation may be important in certain areas.
---
paper_title: Terms for the quantitation of a mixture of stereoisomers.

paper_content:

Various terms for the quantitation of a mixture of enantiomers and diastereomers are discussed.
---
paper_title: Solid-phase extraction combined with dispersive liquid-liquid microextraction and chiral liquid chromatography-tandem mass spectrometry for the simultaneous enantioselective determination of representative proton-pump inhibitors in water samples

paper_content:

This report describes, for the first time, the simultaneous enantioselective determination of proton-pump inhibitors (PPIs-omeprazole, lansoprazole, pantoprazole, and rabeprazole) in environmental water matrices based on solid-phase extraction combined with dispersive liquid-liquid microextraction (SPE-DLLME) and chiral liquid chromatography-tandem mass spectrometry. The optimized results of SPE-DLLME were obtained with PEP-2 column using methanol-acetonitrile (1/1, v/v) as elution solvent, dichloroethane, and acetonitrile as extractant and disperser solvent, respectively. The separation and determination were performed using reversed-phase chromatography on a cellulose chiral stationary phase, a Chiralpak IC (250 mm × 4.6 mm, 5 μm) column, under isocratic conditions at 0.6 mL min(-1) flow rate. The analytes were detected in multiple reaction monitoring (MRM) mode by triple quadrupole mass spectrometry. Isotopically labeled internal standards were used to compensate matrix interferences. The method provided enrichment factors of around 500. Under optimal conditions, the mean recoveries for all eight enantiomers from the water samples were 89.3-107.3 % with 0.9-10.3 % intra-day RSD and 2.3-8.1 % inter-day RSD at 20 and 100 ng L(-1) levels. Correlation coefficients (r (2)) ≥ 0.999 were achieved for all enantiomers within the range of 2-500 μg L(-1). The method detection and quantification limits were at very low levels, within the range of 0.67-2.29 ng L(-1) and 2.54-8.68 ng L(-1), respectively. This method was successfully applied to the determination of the concentrations and enantiomeric fractions of the targeted analytes in wastewater and river water, making it applicable to the assessment of the enantiomeric fate of PPIs in the environment. Graphical Abstract Simultaneous enantioselective determination of representative proton-pump inhibitors in water samples.
---
paper_title: Enantioselective HPLC analysis and biodegradation of atenolol, metoprolol and fluoxetine

paper_content:

The accurate quantification of enantiomers is crucial for assessing the biodegradation of chiral pharmaceuticals in the environment. Methods to quantify enantiomers in environmental matrices are scarce. Here, we used an enantioselective method, high-performance liquid chromatography with fluorescence detection (HPLC-FD), to analyze two beta-blockers, metoprolol and atenolol, and the antidepressant fluoxetine in an activated sludge consortium from a wastewater treatment plant. The vancomycin-based chiral stationary phase was used under polar ionic mode to achieve the enantioseparation of target chiral pharmaceuticals in a single chromatographic run. The method was successfully validated over a concentration range of 20–800 ng/mL for each enantiomer of both beta-blockers and of 50–800 ng/mL for fluoxetine enantiomers. The limits of detection were between 5 and 20 ng/mL and the limits of quantification were between 20 and 50 ng/mL, for all enantiomers. The intra- and inter-batch precision was lower than 5.66 and 8.37 %, respectively. Accuracy values were between 103.03 and 117.92 %, and recovery rates were in the range of 88.48–116.62 %. Furthermore, the enantioselective biodegradation of atenolol, metoprolol and fluoxetine was followed during 15 days. The (S)-enantiomeric form of metoprolol was degraded at higher extents, whereas the degradation of atenolol and fluoxetine did not show enantioselectivity under the applied conditions.
---
paper_title: Use of the chiral pharmaceutical propranolol to identify sewage discharges into surface waters.

paper_content:

The discharge of relatively small volumes of untreated sewage is a source of wastewater-derived contaminants in surface waters that is often ignored because it is difficult to discriminate from wastewater effluent. To identify raw sewage discharges, we analyzed the two enantiomers of the popular chiral pharmaceutical, propranolol, after derivitization to convert the enantiomers to diastereomers. The enantiomeric fraction (the ratio of the concentration of one of its isomers to the total concentration) of propranolol in the influent of five wastewater treatment plants was 0.50 +/- 0.02, while after secondary treatment it was 0.42 or less. In a laboratory study designed to simulate an activated sludge municipal wastewater treatment system, the enantiomeric fraction of propranolol decreased from 0.5 to 0.43 as the compound underwent biotransformation. In a similar system designed to simulate an effluent-dominanted surface water, the enantiomeric fraction of propranolol remained constant as it underwent biotransformation. Analysis of samples from surface waters with known or suspected discharges of untreated sewage contained propranolol with an enantiomeric fraction of approximately 0.50 whereas surface waters with large discharges of wastewater effluent contained propranolol with enantiomeric fractions similar to those observed in wastewater effluent. Measurement of enantiomers of propranolol may be useful in detecting and documenting contaminants related to leaking sewers and combined sewer overflows.
---
paper_title: Enantioselective simultaneous analysis of selected pharmaceuticals in environmental samples by ultrahigh performance supercritical fluid based chromatography tandem mass spectrometry.

paper_content:

In order to assess the true impact of each single enantiomer of pharmacologically active compounds (PACs) in the environment, highly efficient, fast and sensitive analytical methods are needed. For the first time this paper focuses on the use of ultrahigh performance supercritical fluid based chromatography coupled to a triple quadrupole mass spectrometer to develop multi-residue enantioselective methods for chiral PACs in environmental matrices. This technique exploits the advantages of supercritical fluid chromatography, ultrahigh performance liquid chromatography and mass spectrometry. Two coated modified 2.5 μm-polysaccharide-based chiral stationary phases were investigated: an amylose tris-3,5-dimethylphenylcarbamate column and a cellulose tris-3-chloro-4-methylphenylcarbamate column. The effect of different chromatographic variables on chiral recognition is highlighted. This novel approach resulted in the baseline resolution of 13 enantiomers PACs (aminorex, carprofen, chloramphenicol, 3-N-dechloroethylifosfamide, flurbiprofen, 2-hydroxyibuprofen, ifosfamide, imazalil, naproxen, ofloxacin, omeprazole, praziquantel and tetramisole) and partial resolution of 2 enantiomers PACs (ibuprofen and indoprofen) under fast-gradient conditions (<10 min analysis time). The overall performance of the methods was satisfactory. The applicability of the methods was tested on influent and effluent wastewater samples. To the best of our knowledge, this is the first feasibility study on the simultaneous separation of chemically diverse chiral PACs in environmental matrices using ultrahigh performance supercritical fluid based chromatography coupled with tandem mass spectrometry.
---
paper_title: Selective degradation of ibuprofen and clofibric acid in two model river biofilm systems

paper_content:

Abstract A field survey indicated that the Elbe and Saale Rivers were contaminated with both clofibric acid and ibuprofen. In Elbe River water we could detect the metabolite hydroxy-ibuprofen. Analyses of the city of Saskatoon sewage effluent discharged to the South Saskatchewan river detected clofibric acid but neither ibuprofen nor any metabolite. Laboratory studies indicated that the pharmaceutical ibuprofen was readily degraded in a river biofilm reactor. Two metabolites were detected and identified as hydroxy–and carboxy–ibuprofen. Both metabolites were observed to degrade in the biofilm reactors. However, in human metabolism the metabolite carboxy–ibuprofen appears and degrades second whereas the opposite occurs in biofilm systems. In biofilms the pharmacologically inactive stereoisomere of ibuprofen is degraded predominantly. In contrast, clofibric acid was not biologically degraded during the experimental period of 21 days. Similar results were obtained using biofilms developed using waters from either the South Saskatchewan or Elbe River. In a sterile reactor no losses of ibuprofen were observed. These results suggested that abiotic losses and adsorption played only a minimal role in the fate of the pharmaceuticals in the river biofilm reactors.
---
paper_title: Critical evaluation of monitoring strategy for the multi-residue determination of 90 chiral and achiral micropollutants in effluent wastewater.

paper_content:

It is essential to monitor the release of organic micropollutants from wastewater treatment plants (WWTPs) for developing environmental risk assessment and assessing compliance with legislative regulation. In this study the impact of sampling strategy on the quantitative determination of micropollutants in effluent wastewater was investigated. An extended list of 90 chiral and achiral micropollutants representing a broad range of biological and physico-chemical properties were studied simultaneously for the first time. During composite sample collection micropollutants can degrade resulting in the under-estimation of concentration. Cooling collected sub-samples to 4°C stabilised ≥81 of 90 micropollutants to acceptable levels (±20% of the initial concentration) in the studied effluents. However, achieving stability for all micropollutants will require an integrated approach to sample collection (i.e., multi-bottle sampling with more than one stabilisation method applied). Full-scale monitoring of effluent revealed time-paced composites attained similar information to volume-paced composites (influent wastewater requires a sampling mode responsive to flow variation). The option of monitoring effluent using time-paced composite samplers is advantageous as not all WWTPs have flow controlled samplers or suitable sites for deploying portable flow meters. There has been little research to date on the impact of monitoring strategy on the determination of chiral micropollutants at the enantiomeric level. Variability in wastewater flow results in a dynamic hydraulic retention time within the WWTP (and upstream sewerage system). Despite chiral micropollutants being susceptible to stereo-selective degradation, no diurnal variability in their enantiomeric distribution was observed. However, unused medication can be directly disposed into the sewer network creating short-term (e.g., daily) changes to their enantiomeric distribution. As enantio-specific toxicity is observed in the environment, similar resolution of enantio-selective analysis to more routinely applied achiral methods is needed throughout the monitoring period for accurate risk assessment.
---
paper_title: Chiral profiling of azole antifungals in municipal wastewater and recipient rivers of the Pearl River Delta, China

paper_content:

Enantiomeric compositions and fractions (EFs) of three chiral imidazole (econazole, ketoconazole, and miconazole) and one chiral triazole (tebuconazole) antifungals were investigated in wastewater, river water, and bed sediment of the Pearl River Delta, South China. The imidazole pharmaceuticals in the untreated wastewater were racemic to weakly nonracemic (EFs of 0.450-0.530) and showed weak enantioselectivity during treatment in the sewage treatment plant. The EFs of the dissolved azole antifungals were usually different from those of the sorbed azoles in the suspended particulate matter, suggesting different behaviors for the enantiomers of the chiral azole antifungals in the dissolved and particulate phases of the wastewater. The azole antifungals were widely present in the rivers. The bed sediment was a sink for the imidazole antifungals. The imidazoles were prevalently racemic, whereas tebuconazole was widely nonracemic in the rivers. Seasonal effects were observed on distribution and chirality of the azole antifungals. Concentrations of the azole antifungals in the river water were relatively higher in winter than in spring and summer while the EF of miconazole in the river water was higher in summer. The mechanism of enantiomeric behavior of the chiral azole antifungals in the environment warrants further research.
---
paper_title: Fast, simple and efficient supramolecular solvent-based microextraction of mecoprop and dichlorprop in soils prior to their enantioselective determination by liquid chromatography-tandem mass spectrometry.

paper_content:

A simple, sensitive, rapid and economic method was developed for the quantification of enantiomers of chiral pesticides as mecoprop (MCPP) and dichlorprop (DCPP) in soil samples using supramolecular solvent-based microextraction (SUSME) combined with liquid chromatography coupled to mass spectrometry (LC-MS/MS). SUSME has been described for the extraction of chiral pesticides in water, but this is firstly applied to soil samples. MCPP and DCPP are herbicides widely used in agriculture that have two enantiomeric forms (R- and S-) differing in environmental fate and toxicity. Therefore, it is essential to have analytical methods for monitoring individual DCPP and MCPP enantiomers in environmental samples. MCPP and DCPP were extracted in a supramolecular solvent (SUPRAS) made up of dodecanoic acid aggregates, the extract was dried under a nitrogen stream, the two herbicides dissolved in acetate buffer and the aqueous extract directly injected in the LC-MS/MS system. The recoveries obtained were independent of soil composition and age of herbicide residues. The detection and quantitation limits of the developed method for the determination of R- and S-MCPP and R- and S-DCPP in soils were 0.03 and 0.1 ng g(-1), respectively, and the precision, expressed as relative standard deviation (n=6), for enantiomer concentrations of 5 and 100 ng g(-1) were in the ranges 4.1-6.1% and 2.9-4.1%. Recoveries for soil samples spiked with enantiomer concentrations within the interval 5-180 ng g(-1) and enantiomeric ratios (ERs) of 1, 3 and 9, ranged between 93 and 104% with standard deviations of the percent recovery varying between 0.3% and 6.0%. Because the SUPRAS can solubilize analytes through different type of interactions (dispersion, dipole-dipole and hydrogen bonds), it could be used to extract a great variety of pesticides (including both polar and non-polar) in soils.
---
paper_title: Enantioselective biodegradation of pharmaceuticals, alprenolol and propranolol, by an activated sludge inoculum.

paper_content:

Biodegradation of chiral pharmaceuticals in the environment can be enantioselective. Thus quantification of enantiomeric fractions during the biodegradation process is crucial for assessing the fate of chiral pollutants. This work presents the biodegradation of alprenolol and propranolol using an activated sludge inoculum, monitored by a validated enantioselective HPLC method with fluorescence detection. The enantioseparation was optimized using a vancomycin-based chiral stationary phase under polar ionic mode. The method was validated using a minimal salts medium inoculated with activated sludge as matrix. The method was selective and linear in the range of 10-800 ng/ml, with a R²>0.99. The accuracy ranged from 85.0 percent to 103 percent, the recovery ranged from 79.9 percent to 103 percent, and the precision measured by the relative standard deviation (RSD) was <7.18 percent for intra-batch and <5.39 percent for inter-batch assays. The limits of quantification and detection for all enantiomers were 10 ng/ml and 2.5 ng/ml, respectively. The method was successfully applied to follow the biodegradation of the target pharmaceuticals using an activated sludge inoculum during a fifteen days assay. The results indicated slightly higher biodegradation rates for the S-enantiomeric forms of both beta-blockers. The presence of another carbon source maintained the enantioselective degradation pattern while enhancing biodegradation extent up to fourteen percent.
---
paper_title: Simultaneous enantiomeric analysis of pharmacologically active compounds in environmental samples by chiral LC-MS/MS with a macrocyclic antibiotic stationary phase.

paper_content:

This paper presents a multi-residue method for direct enantioselective separation of chiral pharmacologically active compounds in environmental matrices. The method is based on chiral liquid chromatography and tandem mass spectrometry detection. Simultaneous chiral discrimination was achieved with a macrocyclic glycopeptide-based column with antibiotic teicoplanin as a chiral selector working under reverse phase mode. For the first time, enantioresolution was reported for metabolites of ibuprofen: carboxyibuprofen and 2-hydroxyibuprofen with this chiral stationary phase. Moreover, enantiomers of chloramphenicol, ibuprofen, ifosfamide, indoprofen, ketoprofen, naproxen and praziquantel were also resolved. The overall performance of the method was satisfactory in terms of linearity, precision, accuracy and limits of detection. The method was successfully applied for monitoring of pharmacologically active compounds at enantiomeric level in influent and effluent wastewater and in river water. In addition, the chiral recognition and analytical performance of the teicoplanin-based column was critically compared with that of the α1 -acid glycoprotein chiral stationary phase. Copyright © 2017 John Wiley & Sons, Ltd.
---
paper_title: Enantioselective degradation of warfarin in soils

paper_content:

Environmental enantioselectivity information is important to fate assessment of chiral contaminants. Warfarin, a rodenticide and prescription medicine, is a chiral chemical but used in racemic form. Little is known about its enantioselective behavior in the environment. In this study, enantioselective degradation of warfarin in a turfgrass and a groundcover soils was examined in aerobic and ambient temperature conditions. An enantioselective analytical method was established using a novel triproline chiral stationary phase in high performance liquid chromatography. Unusual peak profile patterns, i.e., first peak (S(−)) broadening/second peak (R(+)) compression with hexane (0.1%TFA)/2-propanol (92/8, v/v) mobile phase, and first peak compression/second peak broadening with the (96/4, v/v) mobile phase, were observed in enantioseparation. This unique tunable peak property was leveraged in evaluating warfarin enantioselective degradation in two types of soil. Warfarin was extracted in high recovery from soil using methylene chloride after an aqueous phase basic-acidic conversion. No apparent degradation of warfarin was observed in the sterile turfgrass and groundcover soils during the 28 days incubation, while it showed quick degradation (half-life <7 days) in the nonsterile soils after a short lag period, suggesting warfarin degradation in the soils was mainly caused by micro-organisms. Limited enantioselectivity was found in the both soils, which was the R(+) enantiomer was preferentially degraded. The half-lives in turfgrass soil were 5.06 ± 0.13 and 5.97 ± 0.05 days, for the R(+) and the S(−) enantiomer, respectively. The corresponding values for the groundcover soil were 4.15 ± 0.11 and 4.47 ± 0.08 days. Chirality, 2011. © 2011 Wiley Periodicals, Inc.
---
paper_title: Distinct Enantiomeric Signals of Ibuprofen and Naproxen in Treated Wastewater and Sewer Overflow

paper_content:

Ibuprofen and naproxen are commonly used members of a class of pharmaceuticals known as 2-arylpropionic acids (2-APAs). Both are chiral chemicals and can exist as either of two (R)- and (S)-enantiomers. Enantioselective analyses of effluents from municipal wastewater treatment plants (WWTPs) and from untreated sewage overflow reveal distinctly different enantiomeric fractions for both pharmaceuticals. The (S)-enantiomers of both were dominant in untreated sewage overflow, but the relative proportions of the (R)-enantiomers were shown to be increased in WWTP effluents. (R)-naproxen was below method detection limits (<1 ng.L(-1)) in sewage overflow, but measurable at higher concentrations in WWTP effluents. Accordingly, enantiomeric fractions (EF) for naproxen were consistently 1.0 in sewage overflow, but ranged from 0.7–0.9 in WWTP effluents. Ibuprofen EF ranged from 0.6–0.8 in sewage overflow and receiving waters, and was 0.5 in two WWTP effluents. Strong evidence is provided to indicate that chiral inversion of (S)-2-APAs to produce (R)-2-APAs may occur during wastewater treatment processes. It is concluded that this characterization of the enantiomeric fractions for ibuprofen and naproxen in particular effluents could facilitate the distinction of treated and untreated sources of pharmaceutical contamination in surface waters.
---
paper_title: Trace analysis of fluoxetine and its metabolite norfluoxetine. Part II : Enantioselective quantification and studies of matrix effects in raw and treated wastewater by solid phase extraction and liquid chromatography-tandem mass spectrometry

paper_content:

The isotope-labeled compounds fluoxetine-d5 and norfluoxetine-d5 were used to study matrix effects caused by co-eluting compounds originating from raw and treated wastewater samples, collected in U ...
---
paper_title: A New Chiral Residue Analysis Method for Triazole Fungicides in Water Using Dispersive Liquid-Liquid Microextraction (DLLME)

paper_content:

A rapid, simple, reliable, and environment-friendly method for the residue analysis of the enantiomers of four chiral fungicides including hexaconazole, triadimefon, tebuconazole, and penconazole in water samples was developed by dispersive liquid-liquid microextraction (DLLME) pretreatment followed by chiral high-performance liquid chromatography (HPLC)-DAD detection. The enantiomers were separated on a Chiralpak IC column by HPLC applying n-hexane or petroleum ether as mobile phase and ethanol or isopropanol as modifier. The influences of mobile phase composition and temperature on the resolution were investigated and most of the enantiomers could be completely separated in 20 min under optimized conditions. The thermodynamic parameters indicated that the separation was enthalpy-driven. The elution orders were detected by both circular dichroism detector (CD) and optical rotatory dispersion detector (ORD). Parameters affecting the DLLME performance for pretreatment of the chiral fungicides residue in water samples, such as the extraction and dispersive solvents and their volume, were studied and optimized. Under the optimum microextraction condition the enrichment factors were over 121 and the linearities were 30-1500 µg L(-1) with the correlation coefficients (R(2)) over 0.9988 and the recoveries were between 88.7% and 103.7% at the spiking levels of 0.5, 0.25, and 0.05 mg L(-1) (for each enantiomer) with relative standard deviations varying from 1.38% to 6.70% (n = 6) The limits of detection (LODs) ranged from 8.5 to 29.0 µg L(-1) (S/N = 3).
---
paper_title: Enantiomeric Fraction Determination of 2-Arylpropionic Acids in a Package Plant Membrane Bioreactor

paper_content:

Enantiomeric compositions of three 2-arylpropionic acid (2-APA) drugs, ibuprofen, naproxen, and ketoprofen, were monitored in a membrane bioreactor (MBR) treating municipal effluent in a small rural town in Australia. Specific enantiomers were determined as amide diastereomers using the chiral derivatizing reagent, (R)-1-phenylethylamine (PEA), followed by gas chromatography-tandem mass spectrometry (GC-MS/MS). The six individual enantiomers were quantified by isotope dilution and the enantiomeric fractions (EFs) were determined. Over four separate sampling events, ibuprofen EF ranged from 0.88 to 0.94 (median 0.93) in the influent and 0.38 to 0.40 (median 0.39) in the effluent. However, no significant change in ketoprofen EF was observed, with influent EFs of 0.56-0.60 (median 0.58) and effluent EFs 0.54-0.68 (median 0.56). This is the first report of enantiospecific analysis of ketoprofen in municipal wastewater and it is not yet clear why such different behavior was observed compared to ibuprofen. Naproxen EF was consistently measured at 0.99 in the influent and ranged from 0.86 to 0.94 (median 0.91) in the effluent. This study demonstrates that EF is a relatively stable parameter and does not fluctuate according to concentration or other short-term variables introduced by sampling limitations. The enantiospecific analysis of chiral chemicals presents a promising approach to elucidate a more thorough understanding of biological treatment processes and a potential tool for monitoring the performance of key biological pathways.
---
paper_title: Loadings, trends, comparisons, and fate of achiral and chiral pharmaceuticals in wastewaters from urban tertiary and rural aerated lagoon treatments.

paper_content:

A comparison of time-weighted average pharmaceutical concentrations, loadings and enantiomer fractions (EFs) was made among treated wastewater from one rural aerated lagoon and from two urban tertiary wastewater treatment plants (WWTPs) in Alberta, Canada. Passive samplers were deployed directly in treated effluent for nearly continuous monitoring of temporal trends between July 2007 and April 2008. In aerated lagoon effluent, concentrations of some drugs changed over time, with some higher concentrations in winter likely due to reduced attenuation from lower temperatures (e.g., less microbially mediated biotransformation) and reduced photolysis from ice cover over lagoons; however, concentrations of some drugs (e.g. antibiotics) may also be influenced by changing use patterns over the year. Winter loadings to receiving waters for the sum of all drugs were 700 and 400 g/day from the two urban plants, compared with 4 g/day from the rural plant. Per capita loadings were similar amongst all plants. This result indicates that measured loadings, weighted by population served by WWTPs, are a good predictor of other effluent concentrations, even among different treatment types. Temporal changes in chiral drug EFs were observed in the effluent of aerated lagoons, and some differences in EF were found among WWTPs. This result suggests that there may be some variation of microbial biotransformation of drugs in WWTPs among plants and treatment types, and that the latter may be a good predictor of EF for some, but not all drugs.
---
paper_title: Enantioselective analysis of ibuprofen, ketoprofen and naproxen in wastewater and environmental water samples.

paper_content:

A highly sensitive and reliable method for the enantioselective analysis of ibuprofen, ketoprofen and naproxen in wastewater and environmental water samples has been developed. These three pharmaceuticals are chiral molecules and the variable presence of their individual (R)- and (S)-enantiomers is of increasing interest for environmental analysis. An indirect method for enantioseparation was achieved by the derivatization of the (R)- and (S)-enantiomers to amide diastereomers using (R)-1-phenylethylamine ((R)-1-PEA). After initial solid phase extraction from aqueous samples, derivatization was undertaken at room temperature in less than 5 min. Optimum recovery and clean-up of the amide diastereomers from the derivatization solution was achieved by a second solid phase extraction step. Separation and detection of the individual diastereomers was undertaken by gas chromatography-tandem mass spectrometry (GC-MS/MS). Excellent analyte separation and peak shapes were achieved for the derivatized (R)- and (S)-enantiomers for all three pharmaceuticals with peak resolution, R(s) is in the range of 2.87-4.02 for all diastereomer pairs. Furthermore, the calibration curves developed for the (S)-enantiomers revealed excellent linearity (r(2) ≥ 0.99) for all three compounds. Method detection limits were shown to be within the range of 0.2-3.3 ng L(-1) for individual enantiomers in ultrapure water, drinking water, surface water and a synthetic wastewater. Finally, the method was shown to perform well on a real tertiary treated wastewater sample, revealing measurable concentrations of both (R)- and (S)-enantiomers of ibuprofen, naproxen and ketoprofen. Isotope dilution using racemic D(3)-ibuprofen, racemic D(3)-ketoprofen and racemic D(3)-naproxen was shown to be an essential aspect of this method for accurate quantification and enantiomeric fraction (EF) determination. This approach produced excellent reproducibility for EF determination of triplicate tertiary treated wastewater samples.
---
paper_title: Enantiomeric fraction evaluation of pharmaceuticals in environmental matrices by liquid chromatography-tandem mass spectrometry

paper_content:

Abstract The interest for environmental fate assessment of chiral pharmaceuticals is increasing and enantioselective analytical methods are mandatory. This study presents an enantioselective analytical method for the quantification of seven pairs of enantiomers of pharmaceuticals and a pair of a metabolite. The selected chiral pharmaceuticals belong to three different therapeutic classes, namely selective serotonin reuptake inhibitors (venlafaxine, fluoxetine and its metabolite norfluoxetine), beta-blockers (alprenolol, bisoprolol, metoprolol, propranolol) and a beta 2 -adrenergic agonist (salbutamol). The analytical method was based on solid phase extraction followed by liquid chromatography tandem mass spectrometry with a triple quadrupole analyser. Briefly, Oasis® MCX cartridges were used to preconcentrate 250 mL of water samples and the reconstituted extracts were analysed with a Chirobiotic™ V under reversed mode. The effluent of a laboratory-scale aerobic granular sludge sequencing batch reactor (AGS-SBR) was used to validate the method. Linearity ( r 2 > 0.99), selectivity and sensitivity were achieved in the range of 20–400 ng L −1 for all enantiomers, except for norfluoxetine enantiomers which range covered 30–400 ng L −1 . The method detection limits were between 0.65 and 11.5 ng L −1 and the method quantification limits were between 1.98 and 19.7 ng L −1 . The identity of all enantiomers was confirmed using two MS/MS transitions and its ion ratios, according to European Commission Decision 2002/657/EC. This method was successfully applied to evaluate effluents of wastewater treatment plants (WWTP) in Portugal. Venlafaxine and fluoxetine were quantified as non-racemic mixtures (enantiomeric fraction ≠ 0.5). The enantioselective validated method was able to monitor chiral pharmaceuticals in WWTP effluents and has potential to assess the enantioselective biodegradation in bioreactors. Further application in environmental matrices as surface and estuarine waters can be exploited.
---
paper_title: Stereoselective biodegradation of amphetamine and methamphetamine in river microcosms

paper_content:

Here presented for the first time is the enantioselective biodegradation of amphetamine and methamphetamine in river microcosm bioreactors. The aim of this investigation was to test the hypothesis that mechanisms governing the fate of amphetamine and methamphetamine in the environment are mostly stereoselective and biological in nature. Several bioreactors were studied over the duration of 15 days (i) in both biotic and abiotic conditions, (ii) in the dark or exposed to light and (iii) in the presence or absence of suspended particulate matter. Bioreactor samples were analysed using SPE-chiral-LC-(QTOF)MS methodology. This investigation has elucidated the fundamental mechanism for degradation of amphetamine and methamphetamine as being predominantly biological in origin. Furthermore, stereoselectivity and changes in enantiomeric fraction (EF) were only observed under biotic conditions. Neither amphetamine nor methamphetamine appeared to demonstrate adsorption to suspended particulate matter. Our experiments also demonstrated that amphetamine and methamphetamine were photo-stable. Illicit drugs are present in the environment at low concentrations but due to their pseudo-persistence and non-racemic behaviour, with two enantiomers revealing significantly different potency (and potentially different toxicity towards aquatic organisms) the risk posed by illicit drugs in the environment should not be under- or over-estimated. The above results demonstrate the need for re-evaluation of the procedures utilised in environmental risk assessment, which currently do not recognise the importance of the phenomenon of chirality in pharmacologically active compounds.
---
paper_title: A column-switching method for quantification of the enantiomers of omeprazole in native matrices of waste and estuarine water samples.

paper_content:

Abstract This work reports the use of a two-dimensional liquid chromatography (2D-LC) system for quantification of the enantiomers of omeprazole in distinct native aqueous matrices. An octyl restricted-access media bovine serum albumin column (RAM-BSA C8) was used in the first dimension, while a polysaccharide-based chiral column was used in the second dimension with either ultraviolet (UV–vis) or ion-trap tandem mass spectrometry (IT-MS/MS) detection. An in-line configuration was employed to assess the exclusion capacity of the RAM-BSA columns to humic substances. The excluded macromolecules had a molecular mass in the order of 18 kDa. Good selectivity, extraction efficiency, accuracy, and precision were achieved employing a very small amount (500 μL or 1.00 mL) of native water sample per injection, with detection limits of 5.00 μg L−1, using UV–vis, and 0.0250 μg L−1, using IT-MS/MS. The total analysis time was only 35 min, with no time spent on sample preparation. The methods were successfully applied to analyze a series of waste and estuarine water samples. The enantiomers were detected in an estuarine water sample collected from the Douro River estuary (Portugal) and in an influent sample from the wastewater treatment plant (WWTP) of Sao Carlos (Brazil). As far as we are concerned, this is the first report of the occurrence of (+)-omeprazole and (−)-omeprazole in native aqueous matrices.
---
paper_title: Occurrence and Environmental Behavior of the Chiral Pharmaceutical Drug Ibuprofen in Surface Waters and in Wastewater

paper_content:

Pharmaceutical compounds can reach detectable concentrations in rivers and lakes if production and use are sufficiently large and the compounds show some mobility and persistence in the aquatic environment. In this study, we report on the occurrence and on the enantiomer composition of the chiral pharmaceutical drug ibuprofen (IB) in surface waters and in samples from wastewater treatment plants (WWTPs). Enantioselective gas chroma tography and detection by mass spectrometry/mass spectrometry was used for analysis. IB was present in influents of WWTPs at concentrations of up to 3 μg/L with a high enantiomeric excess of the pharmacologically active S enantiomer (S ≫ R), as from human urinary excretion. The principal human urinary metabolites of IB, hydroxy-IB and carboxy-IB, were observed in WWTP influents at even higher concentrations. In contrast to other pharmaceutical compounds such as clofibric acid and diclofenac, IB and its metabolites are then efficiently degraded (>95%) during treatment in WWTPs. ...
---
paper_title: Direct injection of native aqueous matrices by achiral–chiral chromatography ion trap mass spectrometry for simultaneous quantification of pantoprazole and lansoprazole enantiomers fractions

paper_content:

Abstract A two-dimensional liquid chromatography system coupled to ion-trap tandem mass spectrometer (2DLC-IT–MS/MS) was employed for the simultaneous quantification of pantoprazole and lansoprazole enantiomers fractions. A restricted access media of bovine serum albumin octyl column (RAM-BSA C 8 ) was used in the first dimension for the exclusion of the humic substances, while a polysaccharide-based chiral column was used in the second dimension for the enantioseparation of both pharmaceuticals. The results described here show good selectivity, extraction efficiency, accuracy, and precision with detection limits of 0.200 and 0.150 μg L −1 for the enatiomers of pantoprazole and lansoprazole respectively, while employing a small amount (1.0 mL) of native water sample per injection. This work reports an innovative assay for monitoring work, studies of biotic and abiotic enantioselective degradation and temporal changes of enantiomeric fractions.
---
paper_title: Multi-residue enantiomeric analysis of human and veterinary pharmaceuticals and their metabolites in environmental samples by chiral liquid chromatography coupled with tandem mass spectrometry detection

paper_content:

Enantiomeric profiling of chiral pharmacologically active compounds (PACs) in the environment has hardly been investigated. This manuscript describes, for the first time, a multi-residue enantioselective method for the analysis of human and veterinary chiral PACs and their main metabolites from different therapeutic groups in complex environmental samples such as wastewater and river water. Several analytes targeted in this paper have not been analysed in the environment at enantiomeric level before. These are aminorex, carboxyibuprofen, carprofen, cephalexin, 3-N-dechloroethylifosfamide, 10,11-dihydro-10-hydroxycarbamazepine, dihydroketoprofen, fenoprofen, fexofenadine, flurbiprofen, 2-hydroxyibuprofen, ifosfamide, indoprofen, mandelic acid, 2-phenylpropionic acid, praziquantel and tetramisole. The method is based on chiral liquid chromatography utilising a chiral α1-acid glycoprotein column and tandem mass spectrometry detection. Excellent chromatographic separation of enantiomers (Rs≥1.0) was achieved for chloramphenicol, fexofenadine, ifosfamide, naproxen, tetramisole, ibuprofen and their metabolites: aminorex and dihydroketoprofen (three of four enantiomers), and partial separation (Rs = 0.7-1.0) was achieved for ketoprofen, praziquantel and the following metabolites: 3-N-dechloroethylifosfamide and 10,11-dihydro-10-hydroxycarbamazepine. The overall performance of the method was satisfactory for most of the compounds targeted. Method detection limits were at low nanogram per litre for surface water and effluent wastewater. Method intra-day precision was on average under 20% and sample pre-concentration using solid phase extraction yielded recoveries >70% for most of the analytes. This novel, selective and sensitive method has been applied for the quantification of chiral PACs in surface water and effluent wastewater providing excellent enantioresolution of multicomponent mixtures in complex environmental samples. It will help with better understanding of the role of individual enantiomers in the environment and will enable more accurate environmental risk assessment.
---
paper_title: Trace analysis of fluoxetine and its metabolite norfluoxetine. Part I: development of a chiral liquid chromatography-tandem mass spectrometry method for wastewater samples.

paper_content:

An enantioselective method for the determination of fluoxetine (a selective serotonin reuptake inhibitor) and its pharmacologically active metabolite norfluoxetine has been developed for raw and tr ...
---
paper_title: Enantiomeric fractionation as a tool for quantitative assessment of biodegradation: The case of metoprolol.

paper_content:

An efficient chiral liquid chromatography high resolution mass spectrometry method has been developed for the determination of metoprolol (MTP) and three of its major metabolites, namely O-desmethylmetoprolol (O-DMTP), α-hydroxymetoprolol (α-HMTP) and metoprolol acid (MTPA) in wastewater treatment plant (WWTP) influents and effluents. The optimized analytical method has been validated with good quality parameters including resolution >1.3 and method quantification limits down to the ng/L range except for MTPA. On the basis of this newly developed analytical method, the stereochemistry of MTP and its metabolites was studied over time in effluent/sediment biotic and sterile microcosms under dark and light conditions and in influents and effluents of 5 different WWTPs. MTP stereoselective degradation was exclusively observed under biotic conditions, confirming the specificity of enantiomeric fraction variations to biodegradation processes. MTP was always biotransformed into MTPA with a (S)-enantiomer enrichment. The results of enantiomeric enrichment pointed the way for a quantitative assessment of in situ biodegradation processes due to a good fit (R(2) > 0.98) of the aerobic MTP biodegradation to the Rayleigh dependency in all the biotic microcosms and in WWTPs because both MTP enantiomers followed the same biodegradation kinetic profiles. These results demonstrate that enantiomeric fractionation constitutes a very interesting quantitative indicator of MTP biodegradation in WWTPs and probably in the environment.
---
paper_title: Stereoisomer analysis of wastewater-derived β-blockers, selective serotonin re-uptake inhibitors, and salbutamol by high-performance liquid chromatography–tandem mass spectrometry

paper_content:

Abstract A reversed-phase enantioselective liquid chromatography–tandem mass spectrometry (HPLC-MS-MS) method was developed to measure enantiomer fractions (EF) and concentrations of pharmaceuticals in wastewater. Enantiomer resolution of six β-blockers (atenolol, metoprolol, nadolol, pindolol, propranolol, and sotalol) along with two selective serotonin re-uptake inhibitors (citalopram, fluoxetine) and one β 2 -agonist (salbutamol) was achieved with the Chirobiotic V stationary phase. Analyte recovery averaged 86% in influent and 78% in effluent with limits of detection ranging from 0.2 to 7.5 ng/L. These results represent an improvement in wastewater EF measurement for atenolol, metoprolol and propranolol as well as the first EF measurements of citalopram, fluoxetine, nadolol, pindolol, salbutamol and sotalol in wastewaters. Changes in EF through treatment indicate biologically mediated stereoselective processes were likely occurring during wastewater treatment.
---
paper_title: Source discrimination of drug residues in wastewater: The case of salbutamol.

paper_content:

Abstract Analytical methods used for pharmaceuticals and drugs of abuse in sewage play a fundamental role in wastewater-based epidemiology (WBE) studies. Here quantitative analysis of drug metabolites in raw wastewaters is used to determine consumption from general population. Its great advantage in public health studies is that it gives objective, real-time data about community use of chemicals, highlighting the relationship between environmental and human health. Within a WBE study on salbutamol use in a large population, we developed a procedure to distinguish human metabolic excretion from external source of contamination, possibly industrial, in wastewaters. Salbutamol is mainly excreted as the sulphate metabolite, which is rapidly hydrolyzed to the parent compound in the environment, so this is currently not detected. When a molecule is either excreted un-metabolized or its metabolites are unstable in the environment, studies can be completed by monitoring the parent compound. In this case it is mandatory to assess whether the drug in wastewater is present because of population use or because of a specific source of contamination, such as industrial manufacturing waste. Because commercial salbutamol mainly occurs as a racemic mixture and is stereoselective in the human metabolism, the enantiomeric relative fraction (EFrel) in wastewater samples should reflect excretion, being unbalanced towards one of two enantiomers, if the drug is of metabolic origin. The procedure described involves chiral analysis of the salbutamol enantiomers by liquid chromatography-tandem mass spectrometry (LC–MS-MS) and calculation of EFrel, to detect samples where external contamination occurs. Samples were collected daily between October and December 2013 from the Milano Nosedo wastewater treatment plant. Carbamazepine and atenolol were measured in the sewage collector, as “control” drugs. Salbutamol EFrel was highly consistent in all samples during this three-month period, but a limited number of samples had unexpectedly high concentrations where the EFrel was close to that observed of the un-metabolized, commercially available drug, supporting the idea of an external source of contamination, besides human metabolic excretion. Results showed that, when present, non-metabolic daily loads could be evaluated indicating an average of 4.12 g/day of salbutamol extra load due to non-metabolic sources. The stereoselectivity in metabolism and enantiomeric ratio analysis appears to be a useful approach in WBE studies to identify different sources of drugs in the environment, when no metabolic products are present at useful analytical levels.
---
paper_title: Chiral analysis of metoprolol and two of its metabolites, α-hydroxymetoprolol and deaminated metoprolol, in wastewater using liquid chromatography–tandem mass spectrometry

paper_content:

A LC–MS/MS method for the chiral separation of metoprolol and two of its main metabolites, α-hydroxymetoprolol (α-OH-Met) and deaminated metoprolol (COOH-Met), in environmental water samples has be ...
---
paper_title: Enantioselective simultaneous analysis of selected pharmaceuticals in environmental samples by ultrahigh performance supercritical fluid based chromatography tandem mass spectrometry.

paper_content:

In order to assess the true impact of each single enantiomer of pharmacologically active compounds (PACs) in the environment, highly efficient, fast and sensitive analytical methods are needed. For the first time this paper focuses on the use of ultrahigh performance supercritical fluid based chromatography coupled to a triple quadrupole mass spectrometer to develop multi-residue enantioselective methods for chiral PACs in environmental matrices. This technique exploits the advantages of supercritical fluid chromatography, ultrahigh performance liquid chromatography and mass spectrometry. Two coated modified 2.5 μm-polysaccharide-based chiral stationary phases were investigated: an amylose tris-3,5-dimethylphenylcarbamate column and a cellulose tris-3-chloro-4-methylphenylcarbamate column. The effect of different chromatographic variables on chiral recognition is highlighted. This novel approach resulted in the baseline resolution of 13 enantiomers PACs (aminorex, carprofen, chloramphenicol, 3-N-dechloroethylifosfamide, flurbiprofen, 2-hydroxyibuprofen, ifosfamide, imazalil, naproxen, ofloxacin, omeprazole, praziquantel and tetramisole) and partial resolution of 2 enantiomers PACs (ibuprofen and indoprofen) under fast-gradient conditions (<10 min analysis time). The overall performance of the methods was satisfactory. The applicability of the methods was tested on influent and effluent wastewater samples. To the best of our knowledge, this is the first feasibility study on the simultaneous separation of chemically diverse chiral PACs in environmental matrices using ultrahigh performance supercritical fluid based chromatography coupled with tandem mass spectrometry.
---
paper_title: Critical evaluation of monitoring strategy for the multi-residue determination of 90 chiral and achiral micropollutants in effluent wastewater.

paper_content:

It is essential to monitor the release of organic micropollutants from wastewater treatment plants (WWTPs) for developing environmental risk assessment and assessing compliance with legislative regulation. In this study the impact of sampling strategy on the quantitative determination of micropollutants in effluent wastewater was investigated. An extended list of 90 chiral and achiral micropollutants representing a broad range of biological and physico-chemical properties were studied simultaneously for the first time. During composite sample collection micropollutants can degrade resulting in the under-estimation of concentration. Cooling collected sub-samples to 4°C stabilised ≥81 of 90 micropollutants to acceptable levels (±20% of the initial concentration) in the studied effluents. However, achieving stability for all micropollutants will require an integrated approach to sample collection (i.e., multi-bottle sampling with more than one stabilisation method applied). Full-scale monitoring of effluent revealed time-paced composites attained similar information to volume-paced composites (influent wastewater requires a sampling mode responsive to flow variation). The option of monitoring effluent using time-paced composite samplers is advantageous as not all WWTPs have flow controlled samplers or suitable sites for deploying portable flow meters. There has been little research to date on the impact of monitoring strategy on the determination of chiral micropollutants at the enantiomeric level. Variability in wastewater flow results in a dynamic hydraulic retention time within the WWTP (and upstream sewerage system). Despite chiral micropollutants being susceptible to stereo-selective degradation, no diurnal variability in their enantiomeric distribution was observed. However, unused medication can be directly disposed into the sewer network creating short-term (e.g., daily) changes to their enantiomeric distribution. As enantio-specific toxicity is observed in the environment, similar resolution of enantio-selective analysis to more routinely applied achiral methods is needed throughout the monitoring period for accurate risk assessment.
---
paper_title: Using chiral liquid chromatography quadrupole time-of-flight mass spectrometry for the analysis of pharmaceuticals and illicit drugs in surface and wastewater at the enantiomeric level.

paper_content:

This paper presents and compares for the first time two chiral LC-QTOF-MS methodologies (utilising CBH and Chirobiotic V columns with cellobiohydrolase and vancomycin as chiral selectors) for the quantification of amphetamine, methamphetamine, MDA (methylenedioxyamphetamine), MDMA (methylenedioxymethamphetamine), propranolol, atenolol, metoprolol, fluoxetine and venlafaxine in river water and sewage effluent. The lowest MDLs (0.3-5.0 ng L(-1) and 1.3-15.1 ng L(-1) for river water and sewage effluent respectively) were observed using the chiral column Chirobiotic V. This is with the exception of methamphetamine and MDMA which had lower MDLs using the CBH column. However, the CBH column resulted in better resolution of enantiomers (R(s)=2.5 for amphetamine compared with R(s)=1.2 with Chirobiotic V). Method recovery rates were typically >80% for both methodologies. Pharmaceuticals and illicit drugs detected and quantified in environmental samples were successfully identified using MS/MS confirmation. In sewage effluent, the total beta-blocker concentrations of propranolol, atenolol and metoprolol were on average 77.0, 1091.0 and 3.6 ng L(-1) thus having EFs (Enantiomeric Fractions) of 0.43, 0.55 and 0.54 respectively. In river water, total propranolol and atenolol was quantified on average at <10.0 ng L(-1). Differences in EF between sewage and river water matrices were evident: venlafaxine was observed with respective EF of 0.43 ± 0.02 and 0.58 ± 0.02.
---
paper_title: Multi-residue enantiomeric analysis of pharmaceuticals and their active metabolites in the Guadalquivir River basin (South Spain) by chiral liquid chromatography coupled with tandem mass spectrometry

paper_content:

This paper describes the development and application of a multi-residue chiral liquid chromatography coupled with tandem mass spectrometry method for simultaneous enantiomeric profiling of 18 chiral pharmaceuticals and their active metabolites (belonging to several therapeutic classes including analgesics, psychiatric drugs, antibiotics, cardiovascular drugs and β-agonists) in surface water and wastewater. To the authors' knowledge, this is the first time an enantiomeric method including such a high number of pharmaceuticals and their metabolites has been reported. Some of the pharmaceuticals have never been studied before in environmental matrices. Among them are timolol, betaxolol, carazolol and clenbuterol. A monitoring programme of the Guadalquivir River basin (South Spain), including 24 sampling sites and five wastewater treatment plants along the basin, revealed that enantiomeric composition of studied pharmaceuticals is dependent on compound and sampling site. Several compounds such as ibuprofen, atenolol, sotalol and metoprolol were frequently found as racemic mixtures. On the other hand, fluoxetine, propranolol and albuterol were found to be enriched with one enantiomer. Such an outcome might be of significant environmental relevance as two enantiomers of the same chiral compound might reveal different ecotoxicity. For example, propranolol was enriched with S(-)-enantiomer, which is known to be more toxic to Pimephales promelas than R(+)-propranolol. Fluoxetine was found to be enriched with S(+)-enantiomer, which is more toxic to P. promelas than R(-)-fluoxetine.
---
paper_title: Pharmaceutical trace analysis in aqueous environmental matrices by liquid chromatography-ion trap tandem mass spectrometry.

paper_content:

An analytical method based on solid-phase extraction followed by liquid chromatography tandem mass spectrometry with an ion trap analyser was developed and validated for the quantification of a series of pharmaceutical compounds with distinct physical-chemical characteristics in estuarine water samples. Method detection limits were between 0.03 and 16.4 ng/L. The sensitivity and the accuracy obtained associated with the inherent confirmatory potential of ion trap tandem mass spectrometry (IT-MS/MS) validates its success as an environmental analysis tool. Two MS/MS transitions were used to confirm compound identity. Almost all pharmaceuticals were detected at ng/L level in at least one sampling site of the Douro River estuary, Portugal.
---
paper_title: Loadings, trends, comparisons, and fate of achiral and chiral pharmaceuticals in wastewaters from urban tertiary and rural aerated lagoon treatments.

paper_content:

A comparison of time-weighted average pharmaceutical concentrations, loadings and enantiomer fractions (EFs) was made among treated wastewater from one rural aerated lagoon and from two urban tertiary wastewater treatment plants (WWTPs) in Alberta, Canada. Passive samplers were deployed directly in treated effluent for nearly continuous monitoring of temporal trends between July 2007 and April 2008. In aerated lagoon effluent, concentrations of some drugs changed over time, with some higher concentrations in winter likely due to reduced attenuation from lower temperatures (e.g., less microbially mediated biotransformation) and reduced photolysis from ice cover over lagoons; however, concentrations of some drugs (e.g. antibiotics) may also be influenced by changing use patterns over the year. Winter loadings to receiving waters for the sum of all drugs were 700 and 400 g/day from the two urban plants, compared with 4 g/day from the rural plant. Per capita loadings were similar amongst all plants. This result indicates that measured loadings, weighted by population served by WWTPs, are a good predictor of other effluent concentrations, even among different treatment types. Temporal changes in chiral drug EFs were observed in the effluent of aerated lagoons, and some differences in EF were found among WWTPs. This result suggests that there may be some variation of microbial biotransformation of drugs in WWTPs among plants and treatment types, and that the latter may be a good predictor of EF for some, but not all drugs.
---
paper_title: Enantiomeric fraction evaluation of pharmaceuticals in environmental matrices by liquid chromatography-tandem mass spectrometry

paper_content:

Abstract The interest for environmental fate assessment of chiral pharmaceuticals is increasing and enantioselective analytical methods are mandatory. This study presents an enantioselective analytical method for the quantification of seven pairs of enantiomers of pharmaceuticals and a pair of a metabolite. The selected chiral pharmaceuticals belong to three different therapeutic classes, namely selective serotonin reuptake inhibitors (venlafaxine, fluoxetine and its metabolite norfluoxetine), beta-blockers (alprenolol, bisoprolol, metoprolol, propranolol) and a beta 2 -adrenergic agonist (salbutamol). The analytical method was based on solid phase extraction followed by liquid chromatography tandem mass spectrometry with a triple quadrupole analyser. Briefly, Oasis® MCX cartridges were used to preconcentrate 250 mL of water samples and the reconstituted extracts were analysed with a Chirobiotic™ V under reversed mode. The effluent of a laboratory-scale aerobic granular sludge sequencing batch reactor (AGS-SBR) was used to validate the method. Linearity ( r 2 > 0.99), selectivity and sensitivity were achieved in the range of 20–400 ng L −1 for all enantiomers, except for norfluoxetine enantiomers which range covered 30–400 ng L −1 . The method detection limits were between 0.65 and 11.5 ng L −1 and the method quantification limits were between 1.98 and 19.7 ng L −1 . The identity of all enantiomers was confirmed using two MS/MS transitions and its ion ratios, according to European Commission Decision 2002/657/EC. This method was successfully applied to evaluate effluents of wastewater treatment plants (WWTP) in Portugal. Venlafaxine and fluoxetine were quantified as non-racemic mixtures (enantiomeric fraction ≠ 0.5). The enantioselective validated method was able to monitor chiral pharmaceuticals in WWTP effluents and has potential to assess the enantioselective biodegradation in bioreactors. Further application in environmental matrices as surface and estuarine waters can be exploited.
---
paper_title: Enantiomeric analysis of drugs of abuse in wastewater by chiral liquid chromatography coupled with tandem mass spectrometry.

paper_content:

The manuscript concerns the development and validation of a method for enantiomeric analysis of structurally related amphetamines (amphetamine, methamphetamine, 4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)), ephedrines (ephedrine, pseudoephedrine and norephedrine) and venlafaxine in wastewater by means of chiral chromatography coupled with tandem mass spectrometry. Solid-phase extraction on Oasis HLB sorbent used for sample clean-up and concentration of analytes resulted in very good recoveries accounting for >70%. Signal suppression during MS analysis was negligible for most studied analytes. Resolution of enantiomers of chiral drugs was found to be higher than 1. Preliminary assay validation was undertaken. The mean correlation coefficients of the calibration curves, which were on average higher than 0.997 for all studied analytes, showed good linearity of the method in the studied range. Intra- and inter-day repeatabilities were on average less than 5%. The method quantification limits in wastewater were at low ppt levels and varied from 2.25 to 11.75ng/L. The method was successfully applied for the analysis of raw and treated wastewater samples collected from four wastewater treatment plants. A common occurrence of 1R,2S (-)-ephedrine, 1S,2S (+)-pseudoephedrine and venlafaxine in both raw and treated wastewater samples was observed. Amphetamine, methamphetamine, MDMA and MDEA were also detected in several wastewater samples. The study of enantiomeric fractions of these chiral drugs proved their variable non-racemic composition. The influence of wastewater treatment processes on the enantiomeric composition of chiral drugs was also noted and might indicate enantioselective processes occurring during treatment, although more comprehensive research has to be undertaken to support this hypothesis.
---
paper_title: Multi-residue enantiomeric analysis of human and veterinary pharmaceuticals and their metabolites in environmental samples by chiral liquid chromatography coupled with tandem mass spectrometry detection

paper_content:

Enantiomeric profiling of chiral pharmacologically active compounds (PACs) in the environment has hardly been investigated. This manuscript describes, for the first time, a multi-residue enantioselective method for the analysis of human and veterinary chiral PACs and their main metabolites from different therapeutic groups in complex environmental samples such as wastewater and river water. Several analytes targeted in this paper have not been analysed in the environment at enantiomeric level before. These are aminorex, carboxyibuprofen, carprofen, cephalexin, 3-N-dechloroethylifosfamide, 10,11-dihydro-10-hydroxycarbamazepine, dihydroketoprofen, fenoprofen, fexofenadine, flurbiprofen, 2-hydroxyibuprofen, ifosfamide, indoprofen, mandelic acid, 2-phenylpropionic acid, praziquantel and tetramisole. The method is based on chiral liquid chromatography utilising a chiral α1-acid glycoprotein column and tandem mass spectrometry detection. Excellent chromatographic separation of enantiomers (Rs≥1.0) was achieved for chloramphenicol, fexofenadine, ifosfamide, naproxen, tetramisole, ibuprofen and their metabolites: aminorex and dihydroketoprofen (three of four enantiomers), and partial separation (Rs = 0.7-1.0) was achieved for ketoprofen, praziquantel and the following metabolites: 3-N-dechloroethylifosfamide and 10,11-dihydro-10-hydroxycarbamazepine. The overall performance of the method was satisfactory for most of the compounds targeted. Method detection limits were at low nanogram per litre for surface water and effluent wastewater. Method intra-day precision was on average under 20% and sample pre-concentration using solid phase extraction yielded recoveries >70% for most of the analytes. This novel, selective and sensitive method has been applied for the quantification of chiral PACs in surface water and effluent wastewater providing excellent enantioresolution of multicomponent mixtures in complex environmental samples. It will help with better understanding of the role of individual enantiomers in the environment and will enable more accurate environmental risk assessment.
---
paper_title: Stereoisomer analysis of wastewater-derived β-blockers, selective serotonin re-uptake inhibitors, and salbutamol by high-performance liquid chromatography–tandem mass spectrometry

paper_content:

Abstract A reversed-phase enantioselective liquid chromatography–tandem mass spectrometry (HPLC-MS-MS) method was developed to measure enantiomer fractions (EF) and concentrations of pharmaceuticals in wastewater. Enantiomer resolution of six β-blockers (atenolol, metoprolol, nadolol, pindolol, propranolol, and sotalol) along with two selective serotonin re-uptake inhibitors (citalopram, fluoxetine) and one β 2 -agonist (salbutamol) was achieved with the Chirobiotic V stationary phase. Analyte recovery averaged 86% in influent and 78% in effluent with limits of detection ranging from 0.2 to 7.5 ng/L. These results represent an improvement in wastewater EF measurement for atenolol, metoprolol and propranolol as well as the first EF measurements of citalopram, fluoxetine, nadolol, pindolol, salbutamol and sotalol in wastewaters. Changes in EF through treatment indicate biologically mediated stereoselective processes were likely occurring during wastewater treatment.
---
paper_title: Determination of chiral pharmaceuticals and illicit drugs in wastewater and sludge using microwave assisted extraction, solid-phase extraction and chiral liquid chromatography coupled with tandem mass spectrometry.

paper_content:

This is the first study presenting a multi-residue method allowing for comprehensive analysis of several chiral pharmacologically active compounds (cPACs) including beta-blockers, antidepressants and amphetamines in wastewater and digested sludge at the enantiomeric level. Analysis of both the liquid and solid matrices within wastewater treatment is crucial to being able to carry out mass balance within these systems. The method developed comprises filtration, microwave assisted extraction and solid phase extraction followed by chiral liquid chromatography coupled with tandem mass spectrometry to analyse the enantiomers of 18 compounds within all three matrices. The method was successfully validated for 10 compounds within all three matrices (amphetamine, methamphetamine, MDMA, MDA, venlafaxine, desmethylvenlafaxine, citalopram, metoprolol, propranolol and sotalol), 7 compounds validated for the liquid matrices only (mirtazapine, salbutamol, fluoxetine, desmethylcitalopram, atenolol, ephedrine and pseudoephedrine) and 1 compound (alprenolol) passing the criteria for solid samples only. The method was then applied to wastewater samples; cPACs were found at concentration ranges in liquid matrices of: 1.7ngL(-1) (metoprolol) - 1321ngL(-1) (tramadol) in influent, Language: en
---
paper_title: Risk assessment of the endocrine-disrupting effects of nine chiral pesticides

paper_content:

The increased release of chiral pesticides into the environment has generated interest in the role of enantioselectivity in the environmental fate and ecotoxicological effects of these compounds. However, the information on the endocrine disrupting effects (EDEs) of chiral pesticides is still limited and discrepancies are also usually observed among different assays. In this study, we investigated the enantioselectivity of EDEs via estrogen and thyroid hormone receptors for nine chiral pesticides using in vitro and in silico approaches. The results of the luciferase reporter gene assays showed 7 chiral pesticides possessed enantioselective estrogenic activities and 2 chiral pesticides exerted thyroid hormone antagonistic effects. Proliferation assays in MCF-7 and GH3 cells were also used to verify the results of the dual-luciferase reporter gene assays. At last, the molecular docking results indicated that the enantioselective EDEs of chiral pesticides were partially due to enantiospecific binding affinities with receptors. Our data not only show enantioselective EDEs of nine chiral pesticides, but also would be helpful to better understanding the molecular biological mechanisms of enantioselectivity in EDEs of chiral pesticides.
---
paper_title: Air-water gas exchange of hexachlorocyclohexanes (HCHs) and the enantiomers of α-HCH in Arctic regions

paper_content:

In the summers of 1993 and 1994, air and water samples were taken in the Bering and Chukchi Seas and on a transect across the polar cap to the Greenland Sea to measure the air-sea gas exchange of hexachlorocyclohexanes (HCHs) and the enantiomers of α-HCH. Atmospheric concentrations of α- and γ-HCH have decreased threefold or more since the mid-1980s, whereas concentrations in surface water have shown little change. The saturation state of surface water (water/air fugacity ratio) was determined from the air and water concentrations of HCHs and their Henry's law constants as a function of temperature. Fugacity ratios >1.0 indicated net volatilization of α-HCH in all regions except the Greenland Sea, where concentrations in air and water were close to equilibrium. Net deposition of γ-HCH in the Chukchi Sea was indicated by fugacity ratios <1.0. In other regions, γ-HCH was volatilizing or near air-water equilibrium. Enantioselective degradation of (−)α-HCH was found in surface water of the Bering and Chukchi Seas. The ER was reversed in the Canada Basin and Greenland Sea, where (+)α-HCH was preferentially lost. The same order of enantioselective degradation was seen in air within the marine boundary layer of these regions, which provides direct evidence for sea-to-air transfer of α-HCH.
---
paper_title: Differing estrogenic activities for the enantiomers of o, p'-DDT in immature female rats.

paper_content:

Female rats (20-21 days) were given single intraperitoneal injections of (+/-)-o,p'-DDT, (--)-o,p'-DDT, or (+)-o,p'-DDT. At 18 h their uteri were excised and the estrogen sensitive parameters, uterine wet weight, and uterine glycogen content were measured. For o,p'-DDT, the levo enantiomer is the more active estrogen in immature female rats. Optical resolutions of other racemic environmental xenobiotics may be important in the evaluation of their biological effects.
---
paper_title: Bromocyclen contamination of surface water, waste water and fish from Northern Germany, and gas chromatographic chiral separation

paper_content:

The concentrations of bromocyclen were determined in the water and muscle tissue of trout and bream from the river Stor (northern Germany), to locate the source of this contaminant. The concentrations in water varied between n.d. and 261 pg/L, while in the fish samples concentrations between 0.01 and 0.24 mg/kg fat were determined. In addition, remarkably high concentrations of bromocyclen were found in waste water from sewage plants discharging into the river Stor and at the city of Hamburg. Sewage plants can be, therefore, assumed to be the main source of bromocyclen contamination. This is the first report about the contamination of river water and waste water with bromocyclen. Determination by chiral capillary gas chromatography using a modified cyclodextrin phase showed no significant enantiomeric excess in the water samples, but a preferential degradation of (+)-bromocyclen in the fish muscle tissue of breams.
---
paper_title: Occurrence and Transformation Reactions of Chiral and Achiral Phenoxyalkanoic Acid Herbicides in Lakes and Rivers in Switzerland

paper_content:

The occurrence of chiral and achiral phenoxyalkanoic acid herbicides in lakes and rivers in Switzerland is reported. The compounds most frequently detected were the chiral 2-(4-chloro-2-methylphenoxy)propionic acid (mecoprop, MCPP) and the achiral 4-chloro-2-methylphenoxyacetic acid (MCPA), 2,4-dichlorophenoxyacetic acid (2,4-D), and dicamba, a benzoic acid derivative. The compounds were generally present at concentrations well below the ECE recommended drinking water tolerance level (100 ng/L), even in lakes situated in areas with intense agricultural activities. The chiral 2-(2,4-dichlorophenoxy)propionic acid (dichlorprop, DCPP) was hardly present, and none of the compounds was detected in mountain lakes. In case of MCPP, both enantiomers (R and S) were present, although only the technical material with the R enantiomer (mecoprop-P) is registered and used as a herbicide in Switzerland. Previous studies indicated significant enantiomerization of MCPP and DCPP in soil leading to residues enriched in R en...
---
paper_title: Occurrence and Behavior of Pesticides in Rainwater, Roof Runoff, and Artificial Stormwater Infiltration

paper_content:

To prevent overloading of sewer systems and to ensure sufficient recharging of the groundwater underneath sealed urban areas, collection and artificial infiltration of roof runoff water has become very popular in many countries including Switzerland. However, there is still a considerable lack of knowledge concerning the quality of roof runoff, particularly with respect to the presence of pesticides. In this work, the occurrence and the temporal variations in concentration in rainwater and in roof runoff from different types of roofs (i.e., clay tile roofs, polyester roofs, flat gravel roofs) were determined for the most important members of three widely used classes of pesticides (i.e., triazines, acetamides, phenoxy acids). It is shown that in rain and roof runoff, maximum pesticide concentrations originating primarily from agricultural use occurred during and right after the application periods. Maximum average concentrations for single rain events and total loads per year were, for example, for atrazi...
---
paper_title: Spatial and temporal distribution of chiral pesticides in Calanus spp. from three Arctic fjords.

paper_content:

Concentration and enantiomeric fractions (EFs) of chiral chlorinated pesticides (α-hexachlorocyclohexane (α-HCH), trans-, cis- and oxychlordane) were determined in Arctic zooplankton, mainly Calanus spp. collected in the period 2007-11 from Svalbard fjords and open pack-ice. The temporal and spatial enantiomer distribution varied considerably for all species and chiral pesticides investigated. An overall enantiomeric excess of (+)-oxychlordane (EF 0.53-0.86) were observed. Cis-chlordane was close to racemic (EF 0.46-0.55), while EF for trans-chlordane varied between 0.29 and 0.55, and between 0.38 and 0.59 for α-HCH. The biodegradation potential for trans-chlordane was higher compared to cis-chlordane. The comprehensive statistical evaluation of the data set revealed that the EF distribution of α-HCH was affected by ice cover to a higher extent compared to cis-chlordane. Potential impact from benthic processes on EFs in zooplankton is an interesting feature and should be further investigated. Enantiomeric selective analyses may be a suitable tool for investigations of climate change related influences on Arctic ecosystems.
---
paper_title: Sources of pesticides in surface waters in Switzerland: pesticide load through waste water treatment plants--current situation and reduction potential.

paper_content:

Concentrations of pesticides in Swiss rivers and lakes frequently exceed the Swiss quality goal of 0.1 lg/l for surface waters. In this study, concentrations of various pesticides (e.g., atrazine, diuron, mecoprop) were continuously measured in the effluents of waste water treatment plants and in two rivers during a period of four months. These measurements revealed that in the catchment of Lake Greifensee, farmers who did not perfectly comply with ‘good agricultural practice’ caused at least 14% of the measured agricultural herbicide load into surface waters. Pesticides, used for additional purposes in urban areas (i.e. protection of materials, conservation, etc.), entered surface waters up to 75% through waste water treatment plants. 2002 Elsevier Science Ltd. All rights reserved.
---
paper_title: Enantioselective degradation of metalaxyl in soils: chiral preference changes with soil pH.

paper_content:

Chiral pesticides are often degraded enantio-/stereoselectively in soils. Degradation is typically studied with one or a small number of soils so that it is not possible to extrapolate the findings on chiral preference to other soils. For this study, the fungicide metalaxyl was chosen as a "chiral probe" to investigate its enantioselective degradation in 20 different soils, selected primarily to cover a wide range of soil properties (e.g., acidic/alkaline, aerobic/ anaerobic) rather than to consider soils of agricultural importance. Racemic metalaxyl was incubated in these soils under laboratory conditions, and the degradation of the enantiomers as well as the enantioselective formation/ degradation of the primary major metabolite, metalaxyl acid, was followed over time, using enantioselective GC-MS after ethylation with diazoethane. In aerobic soils with pH > 5, the fungicidally active R-enantiomer was degraded faster than the S-enantiomer (k(R) > k(S)), leading to residues with a composition [S] > [R]. However, in aerobic soils with pH 4-5, both enantiomers were degraded at similar rates (k(R) approximately k(S)), and in aerobic soils with pH < 4 and in most anaerobic soils, the enantioselectivity was reversed (k(R) < k(S)). These considerable soil-to-soil variations were observed with soils from locations close to each other, in one case even within a single soil profile. Liming and acidification of a "nonenantioselective" soil prior to incubation resulted in enantioselective degradation with k(R)> k(S) and k(R) < k(S), respectively. While the enantioselectivity (expressed as ES = (k(R) - k(S))/(k(R) + k(S))) of metalaxyl degradation in aerobic soils apparently correlated with soil pH, no such correlation was found for metalaxyl acid. Reevaluation of published kinetic data for the herbicides dichlorprop and mecoprop indicated similar correlations between soil pH and ES as for metalaxyl.
---
paper_title: Enantioselective and nonenantioselective degradation of organic pollutants in the marine ecosystem

paper_content:

Enantiomeric ratios of 11 chiral environmental pollutants determined in different compartments of the marine ecosystem by chiral capillary gas chromatography and chiral high-performance liquid chromatography allow discrimination between the following processes: enantioselective decomposition of both enantiomers with different velocities by marine microorganisms (α-HCH, β-PCCH, γ-PCCH); enantioselective decomposition of one enantiomer only by marine microorganisms (DCPP); enantioselective decomposition by enzymatic processes in marine biota (α-HCH, β-PCCH, trans-chlordane, cis-chlordane, octachlordane MC4, octachlordane MC5, octachlordane MC7, oxychlordane, heptachlor epoxide); enantioselective active transport through the “blood–brain barrier” (α-HCH); nonenantioselective photochemical degradation (α-HCH, β-PCCH). © 1993 Wiley-Liss, Inc.
---
paper_title: Variations in α-Hexachlorocyclohexane enantiomer ratios in relation to microbial activity in a temperate estuary

paper_content:

Changes in the enantiomer ratios (ERs) of chiral pollutants in the environment are often considered evidence of biological alteration despite the lack of data on causal or mechanistic relationships between microbial parameters and ER values. Enantiomer ratios that deviate from 1:1 in the environment provide evidence for the preferential microbial degradation of one enantiomer, whereas ER values equal to 1 provide no evidence for microbial degradation and may mistakenly be interpreted as evidence that biodegradation is not important. In an attempt to link biological and geochemical information related to enantioselective processes, we measured the ERs of the chiral pesticide α-hexachlorocyclohexane (α-HCH) and bacterial activity (normalized to abundance) in surface waters of the York River (VA, USA) bimonthly throughout one year. Despite lower overall α-HCH concentrations, α-HCH ER values were unexpectedly close to 1:1 in the freshwater region of the estuary with the highest bacterial activity. In contrast, ER values were nonracemic (ER ≠ 1) and α-HCH concentrations were significantly higher in the higher salinity region of the estuary, where bacterial activity was lower. Examination of these data may indicate that racemic environmental ER values are not necessarily reflective of a lack of biodegradation or recent input into the environment, and that nonenantioselective biodegradation may be important in certain areas.
---
paper_title: External exposure and bioaccumulation of PCBs in humans living in a contaminated urban environment.

paper_content:

Humans are exposed to different mixtures of PCBs depending on the route of exposure. In this study we investigated the potential contribution of inhalation to the overall human exposure to PCBs in an urban area. For this purpose, the mechanistically based, non-steady state bioaccumulation model ACC-HUMAN was applied to predict the PCB body burden in an adult living in the Midwestern United States who eats a typical North American diet and inhales air contaminated with PCBs. Dietary exposure was estimated using measured data for eighteen PCB congeners in different food groups (fish, meat and egg, dairy products). Two scenarios for inhalation exposure were evaluated: one using air concentrations measured in Chicago, and a second using air measurements in a remote area on Lake Michigan, Sleeping Bear Dunes. The model predicted that exposure via inhalation increases the accumulated mass of PCBs in the body by up to 30% for lower chlorinated congeners, while diet is by far the dominant source of exposure for those PCB congeners that accumulate most in humans.
---
paper_title: Determination of atropisomeric and planar polychlorinated biphenyls, their enantiomeric fractions and tissue distribution in grey seals using comprehensive 2D gas chromatography

paper_content:

High prevalence of uterine occlusions and sterility is found among Baltic ringed and grey seal. Polychlorinated biphenyls (CBs) are suspected to be the main cause. The CB concentrations are higher in affected than in healthy animals, but the natural variation is considerable. Thus, it might be possible to assess the health status of seals by CB analysis. The ratios of chiral compounds (enantiomeric fractions (EFs)) such as atropisomeric CBs are of particular interest, since these may reflect differences in metabolic rates. An analytical procedure was developed and used to determine the levels of atropisomeric CBs, planar-CBs (WHO-PCBs) and total CBs in seals of different health status. Comprehensive 2D gas chromatography (GC×GC) was used to separate the target analytes from other CBs and interferences and a micro electron-capture detector (μECD) was used for detection. EFs of the atropisomeric CBs were difficult to determine as the levels were low and the interferences many. Two column combinations had to be used to avoid biased results—both had a chiral column as first-dimension column. The second-dimension column was coated with either a high-polarity cyanopropyl or a liquid crystal phase. EFs were determined for five atropisomeric CBs, i.e. CBs 91, 95, 132, 149 and 174. The results were verified by GC×GC–time-of-flight mass spectrometry (TOF-MS). Some atropisomeric CBs had EFs that deviated strongly from the racemic-mixture value. The deviations were larger in liver than blubber, which indicates enantioselective metabolism. However, there was no selective passage of the studied atropisomeric CBs across placenta and no selective blood–brain barrier. Similarly, no correlation between EFs and health status was observed, although there was a correlation between the total CB levels and health status.
---
paper_title: Enantioselective gas chromatography/mass spectrometry of methylsulfonyl PCBs with application to arctic marine mammals.

paper_content:

Four different commercially available cyclodextrin (CD) capillary gas chromatography (GC) columns were tested for the enantioselective separation of nine environmentally persistent atropisomeric 3- and 4-methylsulfonyl PCBs (MeSO2-CBs). The selected columns contained cyclodextrins with various cavity diameters (beta- or gamma-CD), which were methylated and/or tert-butyldimethylsilylated (TBDMS) in the 2,3,6-O-positions. The beta-CD column with TBDMS substituents in all of the 2,3,6-O-positions was by far the most selective column for the MeSO2-CBs tested. Enantiomers of congeners with 3-MeSO2 substitution were more easily separated than those with 4-MeSO2 substitution. The separation also seemed to be enhanced for congeners with the chlorine atoms on the non-MeSO2-containing ring and clustered on one side of the same ring. The 2,3-di-O-methyl-6-O-TBDMS-beta-CD was found to give somewhat better selectivity than the corresponding gamma-CD, in comparison between the two columns, which were identical in all other respects. Enantioselective analysis of arctic ringed seal (Phoca hispida) and polar bear (Ursus maritimus) adipose tissue revealed a strong dominance of certain enantiomers. For example, the enantiomer ratio (ER) of 3-MeSO2-CB149 was 0.32 and < 0.1 in ringed seal blubber and polar bear fat, respectively. These low ER values are indicative of highly enantioselective formation, enantioselective metabolism, enantioselective transport across cell membranes, or a combination of the three in both species. Comparable results for the enantiomeric analysis of MeSO2-CBs in biotic tissue extracts were obtained using two highly selective mass spectrometric techniques, ion trap mass spectrometry/mass spectrometry and electron capture negative ion low-resolution mass spectrometry.
---
paper_title: Metabolism and metabolites of polychlorinated biphenyls.

paper_content:

Abstract The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity, and thereby on the assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general, and in humans in particular. The aim of this document is to provide an overview of PCB metabolism, and to identify the metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed.
---
paper_title: Critical evaluation of monitoring strategy for the multi-residue determination of 90 chiral and achiral micropollutants in effluent wastewater.

paper_content:

It is essential to monitor the release of organic micropollutants from wastewater treatment plants (WWTPs) for developing environmental risk assessment and assessing compliance with legislative regulation. In this study the impact of sampling strategy on the quantitative determination of micropollutants in effluent wastewater was investigated. An extended list of 90 chiral and achiral micropollutants representing a broad range of biological and physico-chemical properties were studied simultaneously for the first time. During composite sample collection micropollutants can degrade resulting in the under-estimation of concentration. Cooling collected sub-samples to 4°C stabilised ≥81 of 90 micropollutants to acceptable levels (±20% of the initial concentration) in the studied effluents. However, achieving stability for all micropollutants will require an integrated approach to sample collection (i.e., multi-bottle sampling with more than one stabilisation method applied). Full-scale monitoring of effluent revealed time-paced composites attained similar information to volume-paced composites (influent wastewater requires a sampling mode responsive to flow variation). The option of monitoring effluent using time-paced composite samplers is advantageous as not all WWTPs have flow controlled samplers or suitable sites for deploying portable flow meters. There has been little research to date on the impact of monitoring strategy on the determination of chiral micropollutants at the enantiomeric level. Variability in wastewater flow results in a dynamic hydraulic retention time within the WWTP (and upstream sewerage system). Despite chiral micropollutants being susceptible to stereo-selective degradation, no diurnal variability in their enantiomeric distribution was observed. However, unused medication can be directly disposed into the sewer network creating short-term (e.g., daily) changes to their enantiomeric distribution. As enantio-specific toxicity is observed in the environment, similar resolution of enantio-selective analysis to more routinely applied achiral methods is needed throughout the monitoring period for accurate risk assessment.
---
paper_title: Enantiomeric composition of chiral polychlorinated biphenyl atropisomers in aquatic bed sediment.

paper_content:

Enantiomeric ratios (ERs) for eight polychlorinated biphenyl (PCB) atropisomers were measured in aquatic sediment from selected sites throughout the United States by using chiral gas chromatography/mass spectrometry. Nonracemic ERs for PCBs 91, 95, 132, 136, 149, 174, and 176 were found in sediment cores from Lake Hartwell, SC, which confirmed previous inconclusive reports of reductive dechlorination of PCBs at these sites on the basis of achiral measurements. Nonracemic ERs for many of the atropisomers were also found in bed-sediment samples from the Hudson and Housatonic Rivers, thus indicating that some of the PCB biotransformation processes identified at these sites are enantioselective. Patterns in ERs among congeners were consistent with known reductive dechlorination patterns at both river sediment basins. The enantioselectivity of PCB 91 is reversed between the Hudson and Housatonic River sites, which implies that the two sites have different PCB biotransformation processes with different enantiom...
---
paper_title: Enantiomeric signatures of chiral polychlorinated biphenyl atropisomers in livers of harbour porpoises (Phocoena phocoena) from the southern North Sea

paper_content:

The enantiomeric composition of polychlorinated biphenyl (PCB) atropisomers, including PCB 95, PCB 149 and PCB 132, was measured in 11 livers of harbour porpoises (Phocoena phocoena) from the southern North Sea. Non-racemic enantiomeric ratios (ERs) were found in some samples. The value of ERs in three of the four juvenile porpoises was equal or almost equal to one, while the ERs in all adults differed from racemic and ranged from 1.31 to 2.54 for PCB 95; from 1.19 to 1.81 for PCB 149 and from 0.45 to 0.94 for PCB 132. There were no relationships between the total concentration of PCBs and ERs. To understand the phenomena, the relationships between the ER value of individual chiral congener with age, concentration of total PCBs and PCB congener pattern were discussed. A model of intake and elimination kinetics was set up and it was tested using the ratio between concentration of PCB 153 and PCB 101 in the liver samples. There was a clear trend between the enantiomeric ratios and the ratio between PCB 153 and PCB 101. Considering that PCB 153 is one of the most persistent PCB congeners in marine mammals and PCB 101 is a relatively easy metabolised congener, this trend means that the enantiomeric ratio most likely reflects the proportion of the metabolised congener. The exposure period in contaminated conditions has a strong impact on ERs, and it is suggested that ERs in wildlife, combined with information on their anthropometric data, health status, diet and habitat conditions, might be good indicators of pollution in coastal ecosystems.
---
paper_title: Multidimensional gas chromatographic separation of selected PCB atropisomers in technical formulations and sediments

paper_content:

A simple dual-column gas chromatographic system with a six-port switching valve has been used to separate the atropisomers of PCB congeners 84, 91, and 95 in technical PCB formulations and in extracts of soil and river sediment. A capillary column coated with a methylphenylsiloxane stationary phase (CP-Sil 8) was used as the first column, for retention window selection, and a permethylated β-cyclodextrin (ChirasilDex) capillary column as the main separation column. Because peak overlap could not be eliminated by optimization of column temperature, the enantiomeric ratios of PCB congeners could not be determined from the original chromatograms. The correct enantiomer ratio was determined from the peak areas obtained by deconvolution of the chromatograms. Whereas the PCB atropisomers considered were present in equal concentrations in the technical PCB formulations, analysis of a river sediment sample confirmed different residual concentrations of the atropisomers of congener 95.
---
paper_title: Enantioselective analysis of chiral polychlorinated biphenyls in sediment samples by multidimensional gas chromatography-electron-capture detection after steam distillation-solvent extraction and sulfur removal

paper_content:

Enantioselective analysis of the chiral polychlorinated biphenyls (PCBs) 95, 132 and 149 in river sediment samples was carried out by multidimensional gas chromatography with an achiral-chiral column combination and electron-capture detection. The investigations revealed the PCB congeners analysed to be present racemic within experimental error. A micro simultaneous steam distillation-solvent extraction device was used as extraction method. This technique proved to be a versatile tool for the extraction of organochlorine compounds from several matrices and was used for the extraction of PCBs from sediment samples. The removal of interfering elementary sulfur was carried out by the treatment with copper powder during the extraction.
---
paper_title: Congener specific determination and enantiomeric ratios of chiral polychlorinated biphenyls in striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea

paper_content:

Blubber and liver samples from six striped dolphins (Stenella coeruleoalba) found dead in the Mediterranean Sea in 1989--1990 were tested for 37 coplanar and chiral polychlorinated biphenyls (PCBs), including the enantiomeric ratios of 9 chiral PCBs. The method includes a fractionation step using HPLC (PYE column) for separating the PCBs according to the number of chlorine atoms in the ortho positions. HRGC/ECD and HRGC/LRMS with an a chiral column (DB-5) were used to determine the PCB congeners. The enantiomeric ratios of nine chiral PCBs were determined by HRGC/LRMS (SIM) with a chiral column (Chirasil-Dex) and by MDGC as the confirmatory technique. The total PCB concentration (sum of 37 congeners) ranged from 7.2 to 89.6 {micro}g/g (wet weight) and from 0.52 to 29.2 {micro}g/g (wet weight) for blubber and liver samples, respectively. PCB profiles were dominated by congeners 138, 153, 170, and 180. The toxic equivalent values (TEQ) ranged from 0.17 to 3.93 ng/g (wet weight) and from 0.02 to 0.73 ng/g (wet weight) for blubber and liver samples, respectively. PCBs 95, 132, 135, 149, and 176 revealed an enantiomeric excess of the second eluted enantiomer in almost all of the samples, whereas PCBs 136 and 174 were racemic or almostmore » racemic. PCBs 88 and 91 were under the detection limits of the methodology used.« less
---
paper_title: Concentrations and enantiomer fractions of organochlorine compounds in Baltic species hit by reproductive impairment

paper_content:

Concentrations and enantiomer fractions (EFs) of organochlorine compounds (OCs) were determined in tissues of gray seal (Halichoerus grypus) and salmon (Salmo salar) originating from the Baltic Sea. The selected seal specimens ranged from starved to unstarved animals, and some of them suffered from a disease complex, while the salmon samples originated from individuals, which were known to produce offspring with and without the M74 syndrome. Significant differences in residue levels and EFs were found between seal groups but not between M74 salmon and non-M74 salmon. The relations between chemical and biological variables of seal samples were investigated with multivariate statistics. Poor health status correlated strongly with age, while bad nutrition condition was associated mainly with high pollution loads and distinctively nonracemic chiral OC compositions. High biotransformation rate (as indicated by fraction of chlordane metabolites in relation to total level of chlordanes) was also associated with large deviations from racemic values and high contaminant levels.
---
paper_title: PCBs and OCPs in human milk in Eastern Siberia, Russia: Levels, temporal trends and infant exposure assessment.

paper_content:

The aim of our study is to investigate the spatial distribution of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (p,p'-DDT) and its metabolites, α- and γ-isomers of hexachlorocyclohexane (HCH) in 155 samples of human milk (HM) from Eastern Siberia (six towns and seven villages in Irkutsk Region, one village of the Republic of Buryatia and one town in Zabaikal'sk Region, Russia), and to examine the dietary and social factors influencing the human exposure to the organochlorines. The median and range of the concentration of six indicator PCBs in HM in 14 localities in Eastern Siberia (114 (19-655) ng g-1 lipids respectively) are similar to levels in the majority of European countries. However, in one village, Onguren, the median and range of levels of six indicator PCBs (1390 (300-3725) ng g-1 lipids) were comparable to levels measured in highly contaminated populations. The Lake Baikal seals are highly exposed to persistent organic pollutants (POPs) and could be a potential source of PCB and DDT exposure in the Onguren cohort via the consumption of the Lake Baikal seal tissue. The location of food production in areas exposed to the emissions of local POP sources can also significantly influence POP levels in HM samples from industrialized areas. Estimated daily intakes (EDI) of HCH and HCB for infants are considerably lower or close to acceptable daily intake (ADI). The EDI of total DDTs and total PCBs are higher than ADI.
---
paper_title: Enantioselective Determination of Polycyclic Musks in River and Wastewater by GC/MS/MS

paper_content:

The separation of chiral compounds is an interesting and challenging topic in analytical chemistry, especially in environmental fields. Enantioselective degradation or bioaccumulation has been observed for several chiral pollutants. Polycyclic musks are chiral and are widely used as fragrances in a variety of personal care products such as soaps, shampoos, cosmetics and perfumes. In this study, the gas chromatographic separation of chiral polycyclic musks, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclo-penta-γ-2-benzopyrane (HHCB), 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetra-hydronaphthalene (AHTN), 6-acetyl-1,1,2,3,3,5-hexamethylindane (AHDI), 5-acetyl-1,1,2,6-tetramethyl-3-iso-propylindane (ATII), and 6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)-indanone (DPMI) was achieved on modified cyclodextrin stationary phase (heptakis (2,3-di-O-methyl-6-O-tert-butyl-dimethylsilyl-β-CD in DV-1701)). Separation techniques are coupled to tandem mass spectrometry (MS-MS), as it provides the sensitivity and selectivity needed. River and wastewaters (influents and effluents of wastewater treatment plants (WWTPs)) in the Nakdong River were investigated with regard to the concentrations and the enantiomeric ratios of polycyclic musks. HHCB was most frequently detected in river and wastewaters, and an enantiomeric enrichment was observed in the effluents of one of the investigated wastewater treatment plants (WWTPs). We reported the contamination of river and wastewaters in Korea by chiral polycyclic musks. The results of this investigation suggest that enantioselective transformation may occur during wastewater treatment.
---
paper_title: A review of personal care products in the aquatic environment: environmental concentrations and toxicity.

paper_content:

Considerable research has been conducted examining occurrence and effects of human use pharmaceuticals in the aquatic environment; however, relatively little research has been conducted examining personal care products although they are found more often and in higher concentrations than pharmaceuticals. Personal care products are continually released into the aquatic environment and are biologically active and persistent. This article examines the acute and chronic toxicity data available for personal care products and highlights areas of concern. Toxicity and environmental data were synergized to develop a preliminary hazard assessment in which only triclosan and triclocarban presented any hazard. However, numerous PCPs including triclosan, paraben preservatives, and UV filters have evidence suggesting endocrine effects in aquatic organisms and thus need to be investigated and incorporated in definitive risk assessments. Additional data pertaining to environmental concentrations of UV filters and parabens, in vivo toxicity data for parabens, and potential for bioaccumulation of PCPs needs to obtained to develop definitive aquatic risk assessments.
---
paper_title: Considerations about the enantioselective transformation of polycyclic musks in wastewater, treated wastewater and sewage sludge and analysis of their fate in a sequencing batch reactor plant.

paper_content:

The present work consists of two distinct parts: in the first part enantioselective GC was used to separate the different enantiomeric/diastereomeric polycyclic musks, PCMs (HHCB, AHTN, AHDI, ATII and DPMI) including the main transformation product of HHCB, HHCB-lactone, in wastewater and sewage sludge. After optimization all PCMs were resolved on a cyclodextrin containing Rt-BDEXcst capillary GC column. Enantiomeric ratios of PCMs in a technical mixture were determined and compared to those obtained from enantioselective separation of wastewater and sewage sludge samples. In general, enantiomeric ratios were similar for most materials in influent, effluent and stabilized sewage sludge. However, the ratios for HHCB, AHDI and particularly ATII suggest some stereospecific removal of these compounds. In the second part, a field study was conducted on a wastewater treatment plant comprising a sequencing batch reactor. Concentrations of HHCB, AHTN, ADBI, AHDI, ATII, DPMI and HHCB-lactone were determined by non-enantioselective GC in daily samples of influent, effluent and activated sludge during one week. Mean concentrations in influent were 6900 and 1520 ng/l for HHCB and AHTN, respectively. The other PCMs exhibited contents 200 ng/l. Mean percent removal was between 61% (AHDI) and 87% (HHCB) resulting in mean effluent concentrations below 860 ng/l. HHCB-lactone concentration increased during wastewater treatment with a mean in the influent of 430 ng/l and in the effluent of 900 ng/l, respectively, indicating a degradation of HHCB.
---

Title: Occurrence of Chiral Bioactive Compounds in the Aquatic Environment: A Review

Section 1: Introduction
Description 1: This section introduces the issue of chiral bioactive compounds in the environment and summarizes the objectives of the review.

Section 2: Basic Concepts of Chirality
Description 2: This section explains the fundamental concepts of chirality, including definitions and implications in an environmental context.

Section 3: Analytical Methodologies for Enantioseparation of Chiral Bioactive Compounds
Description 3: This section provides a review of the chromatographic methods used for the analysis of chiral bioactive drugs in environmental matrices.

Section 4: Chiral Bioactive Compounds of Environmental Concern
Description 4: This section describes reports on the occurrence of various chiral bioactive compounds such as illicit drugs, pharmaceuticals, pesticides, PCBs, and PCMs in aquatic environments.

Section 5: Illicit Drugs and Pharmaceuticals
Description 5: This section focuses on the enantioselective analysis of illicit drugs and pharmaceuticals in environmental matrices, discussing specific compounds and their enantiomeric behaviors.

Section 6: Multi-Class Enantioselective Analysis
Description 6: This section addresses the challenges and methodologies for multi-residue enantioselective analysis of pharmaceuticals and drugs of abuse in environmental samples.

Section 7: Environmental Chiral Analysis of Pesticides, PCBs, and PCMs
Description 7: This section covers the enantioselective occurrence, distribution, and biodegradation of pesticides, PCBs, and PCMs in various environmental matrices.

Section 8: Conclusions
Description 8: This section provides a summary of the findings on the occurrence and environmental impact of chiral bioactive compounds, and suggests areas for future research.