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The aim of this study was to introduce a model to predict pharmaceuticals concentrations in the aquatic environment and their environmental impacts using the Risk Quotient (RQ) approach. The model was trained using: (i) high resolution dataset on pharmaceuticals' concentration in wastewater and receiving environment in a river catchment, (ii) understanding of pharmaceuticals' discharge points in the catchment, (iii) fate of pharmaceuticals during wastewater treatment and in the receiving environment, (iv) high resolution per-postcode pharmaceutical prescription data. A total of 41 pharmaceuticals were evaluated, with successful predictions achieved for concentrations falling within the range of 0.7 (influent: 37 %, effluent: 39 %, river: 29 %) to 1 % (influent: 56 %, effluent: 58 %, river: 48 %) of the measured values. Importantly, our risk assessment demonstrates significant environmental risks associated with specific pharmaceuticals, with strong alignment (86 %) between assessments based on predicted and measured data, underscoring the reliability of our model in assessing environmental risks. The observed variability in predicted and measured concentrations underscores the necessity for ongoing model refinement, particularly in regions with notable discrepancies such as wastewater treatment plant (WWTP) C. Overall, our study illustrates the intricate dynamics of pharmaceutical contamination in aquatic ecosystems, emphasizing the crucial need for continued research in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Water quality management is a pressing global concern, and an increasingly complex issue due to climate and land-use change, legacy pollution, and the persistent release of well-known and emerging contaminants from diffuse and point sources. The increasing availability of high-frequency monitoring data is leading existing, often heuristic approaches, to be judged inadequate. Water managers frequently rely on simple qualitative and/or quantitative approaches for decision-making, but a lack of tangible improvement in freshwater quality outcomes is demanding new and innovative approaches that rely more on physical process understanding, rather than precedent. In this study, we drew upon local geological, hydrogeological, and hydrological data to infer a high-level perceptual model of surface/groundwater interactions in a chalk stream in Dorset, UK. We used the perceptual model to interrogate spatial and temporal trends in historical water quality data and to construct reach-scale nutrient mass balances. Through novel representation with Sankey diagrams, the perceptual model highlighted the relative importance of different hydrological features. Surface/groundwater interactions were found to occur predominantly by spring flow. We demonstrate that river flow accretion was dominated by the Chalk aquifer despite only occupying ca. 15 % of the surface bedrock area, and that spring sources, whilst vital to dilute treated sewage inputs in baseflow conditions, were also major sources of legacy nitrate. Nutrient mass balances showed that sewage treatment works contributed ca. 13 % to soluble reactive phosphorus load, with groundwater accounting for ca. 48 %. Thus, a determinand often associated with point-source pollution was shown to be diffuse dominated in this river. The study demonstrated how a multi-disciplinary approach to water management, based on a comprehensive perceptual modelling approach, could identify hitherto unknown sources and relative contributors to freshwater pollution and allow flow and load apportionment studies to provide useful decision-support to manage nutrient pollution. The novel application of perceptual modelling tools, such as the Sankey diagram, allows different source attributions to be presented in an accessible manner, and can be readily transferred to other study areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This manuscript introduces a new wastewater-based epidemiology workflow for estimation of non-communicable diseases (NCDs) prevalence by using wastewater-based epidemiology (WBE) and pharmaceuticals/their metabolites as proxies for NCDs prevalence. 83 targets were selected (54 parent pharmaceuticals and 29 metabolites). Three critical aspects were tested: (i) Solid-Phase Extraction - Ultra-Performance Liquid Chromatography and Tandem Mass Spectrometry (SPE-UHPLC-MS/MS) method performance, (ii) biomarker stability under variable storage conditions (during sampling and long-term storage) and (iii) accounting for human metabolism in WBE back-calculations. High stability of most analytes was observed under tested storage conditions. A few exceptions include diazepam, dihydroketoprofen and 5-hydroxy-lansoprazole. Analyte recoveries varied between 75% and 125% for most analytes. MDLs ranged from 0.2 ng L -1 to 5.6 ng L -1 , while MQLs from 0.2 ng L -1 to 16.8 ng L -1 . The overall average method accuracy and precision were: 99.5% and 4.0% respectively. A fully validated method was tested using community wastewater in the Southwest of England to estimate pharmaceutical usage, test metabolism correction factors established and compare results with prescription data. The new WBE method for NCD approximation allowed for the estimation of the daily usage/intake of 69 NCD targets with a standardized approach and a consistent reporting format., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Estimation of community-wide consumption of illicit drugs through wastewater analysis is a new concept in Africa although widely applied in developed nations as wastewater-based epidemiology (WBE). It is an important tool that can be used in understanding supply and demand patterns of illicit drug use on a local, national, and international scale. Information on illicit drug use is currently limited in Africa, because of a lack of monitoring structures by governments and financial constraints. This study hopes to bridge that gap by contributing to Africa's baseline information on illicit drug use. This study provides the first application of wastewater analysis to quantitatively evaluate daily illicit drug use in the eThekwini Metropolitan Municipality of KwaZulu-Natal Province of South Africa by quantifying the major urinary excreted metabolites, called drug target residues (DTRs), in raw wastewater from four major wastewater treatment plants (WWTPs) sampled for a week. The results showed that cocaine was the dominant illicit drug consumed in the catchment followed by amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine, with a per capita use of 360-3000 mg day -1 1000 inh -1 , 47-800 mg day -1 1000 inh -1 , 19-120 mg day -1 1000 inh -1 , not detected (ND) to 4.9 mg day -1 1000 inh -1 , and ND to 410 g day -1 1000 inh -1 respectively. The weekly usage patterns between the four WWTPs differed probably due to the lifestyle of the populace serving the different WWTPs. These results provide useful data on illicit drug use in eThekwini that can be utilised by public health agencies to implement suitable response strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There has been a significant increase in antimicrobial agents (AAs) usage, globally - however the relative consumption is unevenly distributed between nations. Inappropriate use of antibiotics can harbour inherent antimicrobial resistance (AMR); therefore, it is important to understand and monitor community-wide prescribing and consumption behaviours throughout different communities around the world. Wastewater-Based Epidemiology (WBE) is a novel tool enabling low cost and large scale studies focussed on AA usage patterns. The back-calculation of community antimicrobial intake was performed from quantities measured in municipal wastewater and informal settlement discharge in the city of Stellenbosch, utilising WBE. Seventeen antimicrobials, and their human metabolites, were evaluated, in concordance with prescription records corresponding to the catchment region. The proportional excretion, biological/chemical stability, and method recovery of each analyte were all crucial factors in the efficacy of the calculation. Mass per day measurements were normalised to the catchment area via population estimates. Municipal wastewater treatment plant population estimates were used to normalise the wastewater samples and prescription data (mg/day/1000 inhabitants). Population estimates for the informal settlements were less accurate due to a lack of reliable sources that were relevant to the sampling time period. Both mass loads and normalised loads suggested higher than average usage throughout the settlements, relative to municipal wastewater. This was seen most prominently in emtricitabine and lamivudine; but also, sulfamethoxazole, trimethoprim, sulfadiazine, clindamycin, ciprofloxacin, ofloxacin, and doxycycline. Urban water fingerprinting (UWF) data triangulation with prescription datasets showed good correlations for several antimicrobial agents (AAs) (e.g., clindamycin, clarithromycin, ofloxacin, and doxycycline). It also revealed discrepancies in usage for some compounds (e.g., tetracycline and sulfapyridine). This might be linked with a lack of pharma compliance in prescription datasets; erroneous association of prescription boundaries with the sewerage catchment; and/or uncertainties within the sewerage catchment (e.g., population estimations). The UWF tool provided a comprehensive overview of multiclass AAs usage, both prescription and over-the counter. For example, tetracycline was not reported in available prescription statistics, but was detected at an average of 18.4 mg/day/1000inh; and no antiviral prescriptions were obtained, but emtricitabine and lamivudine were quantified at 2415.4 and 144.4 mg/day/1000inh, respectively. A lack of clarity regarding prescriptions and a lack of inclusion of several critical (often over-the-counter) medications in public health databases makes WBE a useful and comprehensive epidemiology tool for tracking pharma usage within a catchment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Predicting the concentration of active pharmaceuticals ingredients (API) in the environment using modelling approaches is an important aspect in the assessment of their environmental risk, especially for the API with no or limited analytical detection methods. However, handling, validating, and incorporating diverse datasets, including API prescription/consumption data, metabolism, flow data, removal efficiency during wastewater treatment, and dilution factor for the modelling is often laborious and time-consuming. The aim of this manuscript is to evaluate R/Shiny based tool, PERK, to facilitate automated modelling and reporting predicted environmental concentration (PEC) of a comprehensive set of API in different environmental matrices. PERK helped to calculate PEC in wastewater influent, effluent, and river, and compare with measured environmental concentrations (MEC) for five catchments located in England. Prediction accuracy (PA), the ratio between PEC and MEC, can be also generated with the tool. PERK provides consistent interactive user-interface, enabling user to visualise the results with limited programming knowledge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The study evaluated the presence and fate of various contaminants of emerging concern (CECs) from a South African wastewater treatment works (WWTW) and surface waters located around an urban setting. A total of 45 CECs were quantified from nine sampling locations over an 11-month period. Daily loads (g/day) of the target analytes in the WWTW showed persistence of some CECs, along with population-normalised daily loads (mg/day/1000inh) of pharmaceuticals and drugs of abuse (DOA) that were estimated for the first time in the study area. Multiple chemical markers were recorded in river water located upstream of the WWTW discharge throughout the study period, suggesting a high degree of diffuse pollution from urban communities in the study area that are not connected to sewage networks or where sanitation services are limited. The potential of using defined surface water locations to perform community-wide substance use profiling for non-sewered communities was also explored. Environmental risk characterisation for the WWTW effluent and surface waters throughout the study period provided multiple risk quotients (RQ) for the target list of CECs spanning over various sentinel trophic levels. High risk profiles (RQ > 1.0) with a frequency of exceedance (FoE) larger than 75 % were recorded for several CECs in both WWTW effluent and surface water locations that suggest potential long-term ecological health risk impacts of pollution hotspot areas in the river catchment situated around the urban area. We present challenges in surface water quality within the study area that is relatable, or may even present more challenging, in other low- or middle-income country (LMICs) settings. The study also highlighted some challenges and limitations associated with the much-needed application of wastewater-based epidemiology (WBE) intervention in non-sewered communities that can inform on public health and communal substance use profiles of the entire urban setting., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Barbara Kasprzyk-Hordern reports financial support was provided by Global Challenges Research Fund., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Chemical pollution (including chemicals of emerging concern - CECs) continues to gain increasing attention as a global threat to human health and the environment, with numerous reports on the adverse and sometimes devastating effects upon ecosystems the presence of these chemicals can have. Whilst many studies have investigated presence of CECs in aquatic environments, these studies have been often focused on higher income countries, leaving significant knowledge gaps for many low-middle income countries. This study proposes a new integrated powerless, in-situ multi-mode extraction (iMME) sampler for the analysis of chemicals (105 CECs) and biological (5 genes) markers in water in contrasting settings: an urbanized Avon River in the UK and remote Olifants River in Kruger National Park in South Africa. The overarching goal was to develop a sampling device that maintains integrity of a diverse range of analytes via analyte immobilization using polymeric and glass fibre materials, without access to power supply or cold chain (continuous chilled storage) for sample transportation. Chemical analysis was achieved using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Several mobile CECs showed low stability in river water, at room temperature and typical 24 h sampling/transport time. It is therefore recommended that, in the absence of cooling, environmental water samples are spiked with internal standards on site, immediately after collection and analyte immobilization option is considered, in order to allow fully quantitative analysis. iMME has proven effective in immobilization, concentration and increased stability of CECs at room temperature (and at least 7 days storage) allowing for sample collection at remote locations. The results from the River Avon and Olifants River sampling indicate that the pristine environment of Olifants catchment is largely unaffected by CECs common in the urbanized River Avon in the UK with a few exceptions: lifestyle chemicals (e.g., caffeine, nicotine and their metabolites), paracetamol and UV filters due to tourism and carbamazepine due to its persistent nature. iMME equipped with an additional gene extraction capability provides an exciting new opportunity of comprehensive biochemical profiling of aqueous samples with one powerless in-situ device. Further work is required to provide full integration of the device and comprehensive assessment of performance in both chemical and biological targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Wastewater-based epidemiology (WBE) has potential to identify the epidemiological links between people, animals, and the environment, as part of antimicrobial resistance (AMR) surveillance. In this study, we investigated six wastewater treatment plants (WWTPs) serving six communities located in two regions in Eastern China: Site A in Zhejiang and site B in Jiangsu province to assess the public use of antimicrobial agents (AA). Fifty antimicrobials and 24 of their metabolites were quantified using ultraperformance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-MS/MS). Spatiotemporal trends were established for measured concentrations, daily loads, and population-normalised daily loads. Daily AA mass loads varied between 1.6 g/day and 324.6 g/day reflecting the WWTP scales, with macrolides and β-lactams showing the highest overall environmental burden at 223.7 g/day and 173.7 g/day, respectively. Emissions of antibiotic residues from manufacturing have been observed, with the peak daily load 12-fold higher than the overall load from a community serving a population of over 600,000. Community exposure levels of 225.2 ± 156.2 mg/day/1000 inhabitant and 351.9 ± 133.5 mg/day/1000 inhabitant were recorded in site A and B, respectively. Paired parent-metabolites analysis identified a large proportion (64-78%) of un-metabolised metronidazole and clindamycin at site B, indicating improper disposal of unused drugs either in the community or in livestock production. Consumption levels, calculated via WBE, suggested relatively low antimicrobial usage in Eastern China compared to other areas in China. This first application of WBE in Eastern China to assess the community-wide exposure to AAs has potential to inform regional antimicrobial stewardship., (Copyright © 2022. Published by Elsevier Ltd.)

Increasing usage of antimicrobials is a significant contributor to the emergence and dissemination of antimicrobial resistance. Wastewater-based epidemiology is a useful tool for evaluating public health, via the monitoring of chemical and biological markers in wastewater influent, such as antibiotics. Sixteen antimicrobials and their metabolites were studied: sulfonamides, trimethoprim, metronidazole, quinolones, nitrofurantoin, cyclines, and antiretrovirals. Correction factors (CFs) for human drug excretion, for various drug forms, were determined via a systematic literature review of pharmacokinetic research. Analyte stability was examined over a 24 h study. The estimation of community-wide drug intake was evaluated using the corresponding catchment prescription data. Overall, antimicrobials excreted in an unchanged form were often observed to over-estimate daily intake. This could be attributed to biotransformation, e.g., via glucuronide cleavage, or direct disposal of unused drugs. Acetyl-sulfonamides, trimethoprim, hydroxy-metronidazole, clarithromycin, ciprofloxacin, ofloxacin, tetracycline, and oxytetracycline generally performed well in the estimation of drug intake, relative to prescription records. The low prevalence of quinolone and trimethoprim metabolites, and the low stability of nitrofurantoin, limited the ability to evaluate these metabolites and their respective CFs., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Antimicrobial agent (AA) usage, excretion, and persistence are all important factors in association with the occurrence and dissemination of antimicrobial resistance. Urban water profiling was utilised in the Eerste River catchment (South Africa) to establish AA usage in a region where comprehensive prescription records were not readily available and where portions of the community did not have sufficient access to sanitation. This technique enabled the environmental exposure to be quantified throughout the catchment area and the identification of contamination hotspots. Monitoring occurred over a 11-month period. 812 samples were processed using UPLC-MS/MS for the quantitation of 56 antimicrobials and 26 of their metabolites. Spatiotemporal trends were established, with consideration to community behaviour, seasonal changes, and physiochemical properties of the analytes. The Eerste River samples collected upstream from the town of Stellenbosch had the lowest AA loads (<4 g/day), unafflicted by industrial presence and with only small impact from farming activities. This was followed by sites downstream from a wastewater treatment plant (serving 178 K people). The measurement of low AA loads (influent: 500-800 g/day and effluent 50-100 g/day), indicates a high efficiency of wastewater treatment, allowing for an effective reduction of AA and a lower environmental burden. This is compared to river sites that receive untreated waste from communities in informal settlements (6-12 K people) that are not connected to the sewer infrastructure (with AA levels accounting for 100-600 g/day). Temporal trends exhibited reduced daily loads during the summer to early autumn (Nov-May). This is likely due to seasonal patterns in community health and/or notable changes in rainfall and temperatures at the sampling locations throughout the year. However, weather patterns are also important to consider - particularly for the river sites. South Africa has notable rainfall and temperature seasonality. Antiretrovirals (ARV), emtricitabine and lamivudine, were the most prevalent drugs throughout the monitoring campaign, followed by tuberculosis drugs and sulfonamides. ARVs were, however, effectively reduced via wastewater treatment processes (>97%). This was also the case for beta-lactams, nitrofurantoin, and trimethoprim. The treatment efficacy for other drugs was more variable, that did not appear to have temporal significance., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Down-the-drain disposal of pharmaceuticals remains an overlooked and unrecognized source of environmental contamination that requires nontechnological "at-source" solutions. Monitoring of 31 pharmaceuticals over 7 days in five wastewater treatment plants (WWTPs) serving five cities in South-West UK revealed down-the-drain codisposal of six pharmaceuticals to three WWTPs (carbamazepine and propranolol in city A, sildenafil in city B, and diltiazem, capecitabine, and sertraline in city D), with a one-off record codisposal of estimated 253 pills = 40 g of carbamazepine and estimated 96 pills = 4 g of propranolol in city A accounting for their 10- and 3-fold respective increases in wastewater daily loads. Direct disposal of pharmaceuticals was found to affect the efficiency of wastewater treatment with much higher pharmaceutical removal (decrease in daily load) during "down-the-drain disposal" days. This is due to lack of conjugated glucuronide metabolites that are cleaved during "consumption-only" days, with the release of a parent pharmaceutical counterbalancing its removal. Higher removal of pharmaceuticals during down-the-drain disposal days reduced pharmaceutical loads reaching receiving environment, albeit with significant levels remaining. The estimated daily loads in receiving water downstream from a discharge point accounted for 13.8 ± 3.4 and 2.1 ± 0.2 g day -1 of carbamazepine and propranolol, respectively, during consumption-only days and peaked at 20.9 g day -1 (carbamazepine) and 4.6 g day -1 (propranolol) during down-the-drain disposal days. Actions are needed to reduce down-the-drain disposal of pharmaceuticals. Our recent work indicated that down-the-drain disposal of pharmaceuticals doubled since the last study in 2005, which may be due to the lack of information and messaging that informs people to dispose of unused medicines at pharmacies. Media campaigns that inform the public of how to safely dispose of medicines are key to improving rates of return and reducing pharmaceutical waste in the environment. The environment is a key motivator for returning unused medicines to a pharmacy and so messaging should highlight environmental risks associated with improper disposal.

The COVID-19 outbreak has forced countries to introduce severe restrictive measures to contain its spread. In particular, physical distancing and restriction of movement have had important consequences on human behaviour and potentially also on illicit drug use and supply. These changes can be associated with additional risks for users, in particular due to reduced access to prevention and harm reduction activities. Furthermore, there have been limitations in the amount of data about drug use which can be collected due to restrictions. To goal of this study was to obtain information about potential changes in illicit drug use impacted by COVID-19 restrictions. Wastewater samples were collected in seven cities in the Netherlands, Belgium, Spain and Italy at the beginning of lockdowns (March-May 2020). Using previously established and validated methods, levels of amphetamine (AMP), methamphetamine (METH), MDMA, benzoylecgonine (BE, the main metabolite of cocaine) and 11-nor-9-carboxy-Δ 9 -tetrahydrocannabinol (THC-COOH, main metabolite of tetrahydrocannabinol (THC)) were measured and compared with findings from previous years. Important differences in levels of consumed drugs were observed across the considered countries. Whilst for some substances and locations, marked decreases in consumption could be observed (e.g., 50% decrease in MDMA levels compared to previous years). In some cases, similar or even higher levels compared to previous years could be found. Changes in weekly patterns were also observed, however these were not clearly defined for all locations and/or substances. Findings confirm that the current situation is highly heterogeneous and that it remains very difficult to explain and/or predict the effect that the present pandemic has on illicit drug use and availability. However, given the current difficulty in obtaining data due to restrictions, wastewater analysis can provide relevant information about the situation at the local level, which would be hard to obtain otherwise., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

WBE was applied to evaluate illicit drug (i.e. amphetamine, cocaine, MDMA and methamphetamine), alcohol and tobacco use in three Lithuanian cities in 2018 and 2019. Considerable concentrations of methamphetamine and MDMA were found in the three locations, suggesting a specific Lithuanian consumption pattern. Yet, unexpected high concentrations of amphetamine (>4 μg/L) were detected in two samples of Kaunas in 2018. Through the use of chiral analysis and non-target and suspect drug precursor compound screening, these extreme values were confirmed to be the result of direct disposal of amphetamine in the sewers. Furthermore, substantial alcohol use was measured in the three investigated catchment populations of Lithuania with almost 4 standard drinks/day/inhabitant aged 15+ on average in 2019. For tobacco, an average of 5.6 cigarettes/day/inhabitant aged 15+ in 2019 was reported with large discrepancies between WBE figures and sales data, potentially highlighting illegal trade of tobacco products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The presence and fate of antifungal agents in the environment have hardly been investigated. This is despite the increased usage of antifungal agents and higher prevalence of antifungal resistance. Stereochemistry of antifungal agents has been largely overlooked due to lack of analytical methods enabling studies at the enantiomeric level. This paper introduces a new analytical method for combined separation of achiral and chiral antifungal agents and their metabolites with the utilization of chiral chromatography coupled with triple quadrupole tandem mass spectrometry to enable comprehensive profiling of wide-ranging antifungal agents and their metabolites in environmental matrices. The method showed very good linearity and range (r 2 > 0.997), method accuracy (61-143%) and precision (3-31%) as well as low (ng L -1 ) MQLs for most analytes. The method was applied in selected environmental samples. The following analytes were quantified: fluconazole, terbinafine, N-desmethyl-carboxyterbinafine, tebuconazole, epoxiconazole, propiconazole and N-deacetyl ketoconazole. They were predominantly present in the aqueous environment (as opposed to wastewater) with sources linked with animal and plant protection rather than usage in humans. Interestingly, chiral fungicides quantified in river water were enriched with one enantiomer. This might have consequences in terms of their ecological effects which warrants further study.

This is the first study of broad range of chemical classes CECs conducted in the upper Wisla river catchment including the biggest WWTPs in this region and surface waters. The list of compounds is extensive and the paper provides, for the first time, better understanding of environmental burden from PCPCs in Poland. Cumulative contribution of hypertension pharmaceuticals, nonsteroidal anti-inflammatory drugs (NSAIDs) and lifestyle chemicals was 89% and 95% in wastewater influent, and 75% in wastewater effluent at both WWTPs. Significant removal efficiencies, exceeding 90%, were found for parabens, UV filters, NSAIDs, steroid estrogens, plasticizers, antibacterials/antibiotics, stimulants and metabolites and lifestyle chemicals. The comparison of the average mass loads of CECs between the influent and effluent, has shown that 27% and 29% of all detected CECs were removed by less than 50%. An increase of concentrations of CECs in the effluent was observed for 18% and 20% of all detected CECs in Kujawy and Plaszow WWTPs, respectively. Negative mass balances of fexofenadine, venlafaxine, o-desmethyltramadol, ketamine and temazepam were noted within WWTPs, which are a result of dissolution of persistent contaminants accumulated in aggregates and/or back-transformation or de-conjugation of metabolites into parent compounds. 44 CECs were detected in surface waters located upstream and downstream of the WWTPs. The concentrations of compounds were largely dependent on the dilution factor of WWTP discharge. The risk quotation (RQ) values for compounds present in surface waters were calculated in relation to their potential for bioaccumulation. Among compounds with high potential for bioaccumulation, with log K OW  ≥ 4.5, diclofenac, atorvastatin and triclosan were found to be of high risk. Many CECs with high, moderate or even low environmental impact have shown high potential for bioaccumulation and should be considered as priority at the same risk level. Moreover, possible synergistic action is still of concern., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Wastewater-based epidemiology (WBE) can be a useful tool to face some of the existing challenges in monitoring the use of new psychoactive substances (NPS), as it can provide objective and updated information. This Europe-wide study aimed to verify the suitability of WBE for investigating the use of NPS. Selected NPS were monitored in urban wastewater by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The main classical illicit drugs were monitored in the same samples to compare their levels with those of NPS. Raw composite wastewater samples were collected in 2016 and 2017 in 14 European countries (22 cities) following best practice sampling protocols. Methcathinone was most frequent (>65% of the cities), followed by mephedrone (>25% of the cities), and only mephedrone, methcathinone and methylone were found in both years. This study depicts the use of NPS in Europe, confirming that it is much lower than the use of classical drugs. WBE proved able to assess the qualitative and quantitative spatial and temporal profiles of NPS use. The results show the changeable nature of the NPS market and the importance of large WBE monitoring campaigns for selected priority NPS. WBE is valuable for complementing epidemiological studies to follow rapidly changing profiles of use of drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This paper explores the strong potential of chemical mining of wastewater for markers of community-wide intake of wide-ranging harmful chemicals belonging to several usage groups: industrial chemicals, personal care products, pesticides, illicit drugs, lifestyle chemicals and prescription pharmaceuticals as a proxy for multi-chemical community-wide exposure. An estimation of chemical intake in five contrasting town/cities based in the Avon River catchment in the South-West UK was undertaken. High-resolution spatiotemporal pharmaceutical prescription databases were used for system calibration, both in terms of biomarker selection and its correction factor, as well as for the overall system performance evaluation, both spatially and temporality. Only metabolism data accounting for phase two metabolism provided correct estimates of pharma intake. Using parent compounds as XCRs (xenobiotic compounds residue) was found to overestimate exposure due to an inclusion of directly disposed (unused) drugs. Spatiotemporal trends in XC intake were observed as a result of occupational exposure (higher bisphenol A (BPA) intake during weekday), and lifestyle choices (higher cocaine and pyrethroid pesticides intake during weekend). WBE is not intended to estimate individual exposure to chemicals. It can however provide estimates at a community level, and as a result, it has the potential to be developed into an early warning system, a powerful tool for large scale screening studies identifying communities at risk and in need of high resolution individual testing at a localised scale., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study provided a holistic understanding of the sources, fate and behaviour of 142 compounds of emerging concern (CECs) throughout a river catchment impacted by 5 major urban areas. Of the incoming 169.3 kg d -1 of CECs entering the WwTWs, 167.9 kg d -1 were present in the liquid phase of influent and 1.4 kg d -1 were present in the solid phase (solid particulate matter, SPM). Analysis of SPM was important to determine accurate loads of incoming antidepressants and antifungal compounds, which are primarily found in the solid phase. Furthermore, these classes and the plasticiser, bisphenol A (BPA) were the highest contributors to CEC load in digested solids. Population normalised loads showed little variation across the catchment at 154 ± 12 mg d -1 inhabitant -1 indicating that population size is the main driver of CECs in the studied catchment. Across the catchment 154.6 kg d -1 were removed from the liquid phase during treatment processes. CECs discharged into surface waters from individual WwTWs contributed between 0.19 kg d -1 at WwTW A to 7.3 kg d -1 at WwTW E, which correlated strongly with the respective contributing populations. Spatial and temporal variations of individual CECs and their respective classes were found in WwTW influent (both solid (influent SPM ) and liquid phases (influent AQ )) throughout the catchment, showing that different urban areas impact the catchment in different ways, with key variables being lifestyle, use of over-the-counter pharmaceuticals and industrial activity. Understanding of both spatial and temporal variation of CECs at the catchment level helped to identify possible instances of direct disposal, as in the case of carbamazepine. Analysis of surface waters throughout the catchment showed increasing mass loads of CECs from upstream of WwTW A to downstream at WwTW D, showing clear individual contributions from WwTWs. Many CECs were ubiquitous throughout the river water in the catchment. Daily loads ranged from 0.005 g d -1 (ketamine, WwTW A) up to 1890.3 g d -1 (metformin, WwTW C) for the 84/138 CECs that were detected downstream of the WwTWs. For metformin this represents the equivalent of ∼1,890 tablets (1,000 mg per tablet) dissolved in the river water downstream of WwTW C., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This paper reports the application of wastewater-based epidemiology (WBE) for the monitoring of one city in the UK in years 2014-2018 as a means of 1) exploring relative temporal changes of illicit drug usage trends across 5 sampling weeks in 5 years, (2) assessing policy impact in reducing drug consumption, focussing particularly on mephedrone, which was classified as a class B drug in the UK in 2010, and the effects of subsequent regulation such as the novel psychoactive substances (NPS) bill of 2016, (3) investigating temporal changes in consumption of prescription pharmaceuticals vs illicit drug usage, and (4) comparing consumption of prescription drugs with WBE to enable more accurate verification of prescription drugs with abuse potential. Mephedrone was quantified only for the first two years of the study, 2014-2015, and remained undetected for the next three years of the study. This shows that given enough time changes in drug policy can have an effect on drug consumption. However, after the introduction of the 2016 NPS bill, between the third and fourth study years, there was an observable increase in the consumption of "classic" drugs of abuse such as cocaine, MDMA and ketamine suggesting a shift away from novel psychoactives. The unique prescription dataset allowed for a more accurate calculation of heroin consumption using morphine by examining other sources morphine. Additionally, for compounds with controlled prescription like methadone, trends in consumption estimated by wastewater and trends in prescription correlated. Wastewater-based epidemiology is a powerful tool for examining whole populations and determining the efficacy and direction of government actions on health, as it can, alongside prescription and wider monitoring data, provide a clear insight into what is being consumed by a population and what action is needed to meet required goals., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study provides an insight into the prevalence of (fluoro)quinolones (FQs) and their specific quinolone qnrS resistance gene in the Avon river catchment area receiving treated wastewater from 5 wastewater treatment plants (WWTPs), serving 1.5 million people and accounting for 75% of inhabitants living in the catchment area in the South West of England.. Ofloxacin, ciprofloxacin, nalidixic acid and norfloxacin were found to be ubiquitous with daily loads reaching a few hundred g/day in wastewater influent and tens of g/day in receiving waters. This was in contrast to other FQs analysed: flumequine, nadifloxacin, lomefloxacin, ulifloxacin, prulifloxacin, besifloxacin and moxifloxacin, which were hardly quantified. Enantiomeric profiling revealed that ofloxacin was enriched with the S-(-)-enantiomer, likely deriving from its prescription as the more potent enantiomerically pure levofloxacin, alongside racemic ofloxacin. While ofloxacin's enantiomeric fraction (EF) remained constant, high stereoselectivity was observed in the case of its metabolite ofloxacin-N-oxide. The removal efficiency of quinolones during wastewater treatment at 5 WWTPs utilising either trickling filters (TF) or activated sludge (AS), was compound and wastewater treatment process dependent, with AS providing better efficiency than TF. The qnrS resistance gene was ubiquitous in wastewater. Its removal was WWTP treatment process dependent with TF performing best and resulting in significant removal of the gene (from 28 to 75%). AS underperformed with only 9% removal in the case of activated sludge and actual increase in the gene copy number within sequencing batch reactors (SBRs). Interestingly, the data suggests that higher removal of antibiotics could be linked with high prevalence of the gene (SBR and WWTP E) and vice versa, low removal of antibiotic is correlated with lower prevalence of the gene in wastewater effluent (TF, WWTP B and D). This is especially prominent in the case of ofloxacin and could indicate that AS might be facilitating antimicrobial resistance (AMR) prevalence to higher extent than TF. Wastewater-based epidemiology (WBE) was also applied to monitor any potential misuse (e.g. direct disposal) of FQs in the catchment. In most cases higher use of antibiotics with respect to official statistics (i.e. ciprofloxacin, ofloxacin) was observed, which suggests that FQs management practice require further attention., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Chiral pharmaceutically active compounds (cPACs) are not currently governed by environmental regulation yet are expected to be in the future. As cPACs can exert stereospecific toxicity in the aquatic environment, it is essential to better understand their stereoselective behaviour here. Therefore, this study aims to provide a new perspective towards comprehensive evaluation of cPACs at a river catchment level, including their stereochemistry as a chemical phenomenon driving fate of chiral molecules in the environment. A large spatial and temporal monitoring program was performed in Southwest England. It included 5 sewage treatment works and the receiving waters of the largest river catchment in Southwest England. Simultaneously, lab-scale microcosm studies in simulated activated sludge bioreactors and river water microcosm were performed to evaluate stereoselective degradation of cPACs. A multi-residue enantioselective method allowed the analysis of a total of 18 pairs of enantiomers and 3 single enantiomers in wastewater and river water samples. Our monitoring program revealed: (1) spatial and temporal variations of cPACs in influent wastewaters resulting from different patterns of usage as well as an (2) enantiomeric enrichment of cPACs, likely due to human metabolism, despite their commercialization as racemic mixtures. A similar chiral signature was observed in effluent and receiving waters. Stereoselective degradation was observed in trickling filters (TF) for naproxen, ketoprofen, cetirizine and 10,11-dihydroxy-10-hydroxycarbamazepine, in sequencing batch reactors (SBR) for ifosfamide and in activated sludge (AS) for cetirizine. The extent of enantiomer-specific fate was wastewater treatment dependent in the case of naproxen (TF showed higher stereoselectivity than AS and SBR) and cetirizine (TF and AS showed higher stereoselectivity than SBR) due to differing microbial population. Furthermore, stereoselective degradation of naproxen was highly variable among STWs using similar treatments (TF) and operating in the same region. Microbial stereoselective degradation was also confirmed by both activated and river water simulated microcosm for chloramphenicol, ketoprofen, indoprofen, naproxen and 10,11-dihydroxy-10-hydroxycarbamazepine. Results from our large scale river catchment monitoring study and lab simulated microcosm show wide-ranging implications of enantiomerism of cPACs on environmental risk assessment (ERA). As two enantiomers of the same compound show different biological effects (e.g. toxicity), their non-racemic presence in the environment might lead to inaccurate ERA. This is because current ERA approaches do not require analysis at enantiomeric level., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Molecular epidemiology in human biomonitoring allows for verification of public exposure to chemical substances. Unfortunately, due to logistical difficulties and high cost, it evaluates only small study groups and as a result does not provide comprehensive large scale community-wide exposure data. Wastewater fingerprinting utilizing metabolic biomarkers of exposure that are excreted collectively by studied populations into urine and ultimately into the community's wastewater, provides a timely alternative to traditional approaches. This study aimed to provide comprehensive spatiotemporal community-wide exposure to bisphenol A (BPA, including BPA intake) using wastewater fingerprinting. Wastewater fingerprinting was undertaken using high resolution mass spectrometry retrospective data mining of characteristic BPA human metabolism marker (bisphenol A sulphate), applied to a large geographical area of 2000 km 2 and a population of ~1.5 million served by 5 WWTPs (wastewater treatment plants) accounting for >75% of the overall population in the studied catchment. Community-wide BPA intake was found to be below temporary tolerable daily intake (t-TDI) level of 4 μg kg -1  day -1 set by the European Food Safety Agency (EFSA) suggesting overall low exposure at 3 WWTPs serving residential areas with low industrial/commercial presence. However, at two WWTPs serving communities with higher industrial/commercial presence, higher BPA sulphate loads corresponding to higher (up to 14 times) BPA intakes (exceeding 10 μg kg -1  day -1 at one WWTP and reaching 50 μg kg -1  day -1 at the second WWTP) were observed and they are likely linked with occupational exposure. Characteristic temporal variations of BPA intake were noted in most studied WWTPs with the lowest intake occurring during weekends and the highest during weekdays., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reported herein is the development of an analytical method for the detection of four oxidative stress biomarkers in wastewater using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) and solid phase extraction (SPE). The following four biomarkers of oxidative stress and lipid peroxidation have been investigated: hydroxynonenal-mercapturic acid (HNE-MA), 8-iso-prostglandin F2beta (8-iso-PGF 2β ), 8-nitroguanine (8-NO 2 Gua) and 8-hydroxy-2-deoxyguanosine (8-OHdG). The method showed very good performance: accuracy (> 87%), precision (> 90%), method quantification limits (1.3-3.0 ng L -1 ) and biomarker stability in wastewater in the case of HNE-MA, 8-OHdG and 8-iso-PGF 2β . In contrast, 8-NO 2 Gua was found to be less stable in wastewater, which affected its method performance: accuracy (> 63%), precision (> 91%) and method quantification limits (85.3 ng L -1 ). Application of the developed method resulted in, for the first time, HNE-MA being successfully observed and quantified within wastewater over a study period of a week (displayed average daily loads per capita of 48.9 ± 4.1 mg/1000/people/day). 8-iso-PGF 2β was detected with good intensity but could not be quantified due to co-elution with other isomers. 8-OHdG was detected, albeit at < MQL. This study demonstrates the potential for expanding on the possible endogenous biomarkers of health used in urban water fingerprinting to aid in measuring health in near-real time on a community-wide scale.

The plasticizer bisphenol-A (BPA) is common to municipal wastewaters and can exert toxicity to exposed organisms in the environment. Here BPA concentration at 5 sewage treatment works (STW) and distribution throughout a river catchment in South West UK were investigated. Sampling sites included influent and effluent wastewater (n = 5), river water (n = 7) and digested sludge (n = 2) which were monitored for 7 consecutive days. Findings revealed average BPA loads in influent wastewater at two STWs were 10-37 times greater than the other wastewaters monitored. Concentrations up to ~100 μg L -1 were measured considerably higher than previously reported for municipal wastewaters. Temporal variability throughout the week (i.e., highest concentrations during weekdays) suggests these high concentrations are linked with industrial activity. Despite ≥90% removal during wastewater treatment, notable concentrations remained in tested effluent (62-892 ng L -1 ). However, minimal impact on BPA concentrations in river water was observed for any of the effluents. The maximum BPA concentration found in river water was 117 ng L -1 which is considerably lower than the current predicted no effect concentration of 1.6 μg L -1 . Nevertheless, analysis of digested sludge from sites which received these elevated BPA levels revealed average concentrations of 4.6 ± 0.3 and 38.7 ± 5.4 μg g -1 . These sludge BPA concentrations are considerably greater than previously reported and are attributed to the high BPA loading in influent wastewater. A typical sludge application regime to agricultural land would result in a predicted BPA concentration of 297 ng g -1 in soil. Further studies are needed on the toxicological thresholds of exposed terrestrial organisms in amended soils to better assess the environmental risk here., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This manuscript presents a comprehensive analytical framework for identification and quantification of chemically diverse endocrine disrupting chemicals (EDCs) used in personal care and consumer products in diverse solid and liquid environmental matrices with an ultimate goal of evaluating public exposure to EDCs via water fingerprinting. Liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry (UHPLC-ESI-MS/MS) was used for targeted analysis of selected EDCs as well as to identify and quantify a few metabolites using post-acquisition data mining. Solid-phase extraction (SPE) was applied to liquid matrices in order to reduce matrix effects and provide required sample concentration and ultimately, high sensitivity and selectivity of measurements. SPE recoveries in liquid samples ranged from 49 to 140% with method quantification limits not exceeding 1 ng L -1 for the majority of EDCs. Microwave-assisted extraction (MAE) was applied to solid samples and when followed by SPE, it permitted the analysis of EDCs in digested sludge. MAE/SPE recoveries varied from 11 to 186% and MQLs between 0.03 and 8.1 ng g -1 with the majority of compounds showing MQLs below 2 ng g -1 . Mass error for quantifier and qualifier ions was below 5 ppm when analysing river water and effluent wastewater and below 10 ppm when analysing influent wastewater and solid samples. The method was successfully applied to environmental samples, with 33 EDCs identified and quantified in wastewater and receiving waters. In addition, several EDCs were found in digested sludge, which confirms that for a more comprehensive understanding of exposure patterns and environmental impact, analysis of solids cannot be neglected. Finally, post-acquisition data mining permitted the identification and quantification of a metabolite of BPA and the identification of a metabolite of 4-Cl-3-methylphenol. Graphical abstract ᅟ.

This paper aims to examine the multiresidue enantiomeric profiling of (fluoro)quinolones and their metabolites in solid and liquid environmental matrices using chiral HPLC-MS/MS method and a CHIRALCEL ® OZ-RH column. Simultaneous chiral separation was obtained for chiral ofloxacin and its main metabolites ofloxacin-N-oxide and desmethyl-ofloxacin; moxifloxacin; the prodrug prulifloxacin and its active compound ulifloxacin; flumequine; nadifloxacin and R-(+)-besifloxacin. Achiral antibiotics (ciprofloxacin, norfloxacin and nalidixic acid) were also included in the method to enable the analysis of all targeted quinolones within one analytical run. Satisfactory enantiomeric resolution (Rs ≥ 1) was obtained for five out of eight chiral drugs enabling quantitative analysis. The overall performance of the method was satisfactory with a method precision <20%, relative recoveries >70% for most of the analytes and method detection limits (MDL) at low ng L -1 levels (0.1 < MDL (ng L -1 )< 6.4, 0.1 < MDL (ng L -1 )< 6.6 and 0.1 < MDL (ng L -1 )< 7.0 in influent, effluent and river waters for 83% compounds, 0.01 < MDL (ng g -1 )< 4.9 in solids for 91% compounds). Enantiomeric profiling from a week-long monitoring campaign in the UK showed that (±)-ofloxacin was found to be racemic in upstream waters but it was enriched with S-(-)-enantiomer in wastewater and in receiving waters. This could be due to the fact that ofloxacin can be used both as a racemate and as a S-(-)-enantiomer. Its consumption was further confirmed by the chiral signature of the investigated ofloxacin metabolites. As a result, alterations in the enantiomeric composition of antibiotics could influence not only their activity and toxicity in the environment, but also could induce changes in the microbial communities constantly exposed to them., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this work a step forward in investigating the use of prescription drugs, namely erectile dysfunction products, at European level was taken by applying the wastewater-based epidemiology approach. 24-h composite samples of untreated wastewater were collected at the entrance of eight wastewater treatment plants serving the catchment within the cities of Bristol, Brussels, Castellón, Copenhagen, Milan, Oslo, Utrecht and Zurich. A validated analytical procedure with direct injection of filtered aliquots by liquid chromatography-tandem mass spectrometry was applied. The target list included the three active pharmaceutical ingredients (sildenafil, tadalafil and vardenafil) together with (bio)transformation products and other analogues. Only sildenafil and its two human urinary metabolites desmethyl- and desethylsildenafil were detected in the samples with concentrations reaching 60 ng L -1 . The concentrations were transformed into normalized measured loads and the estimated actual consumption of sildenafil was back-calculated from these loads. In addition, national prescription data from five countries was gathered in the form of the number of prescribed daily doses and transformed into predicted loads for comparison. This comparison resulted in the evidence of a different spatial trend across Europe. In Utrecht and Brussels, prescription data could only partly explain the total amount found in wastewater; whereas in Bristol, the comparison was in agreement; and in Milan and Oslo a lower amount was found in wastewater than expected from the prescription data. This study illustrates the potential of wastewater-based epidemiology to investigate the use of counterfeit medication and rogue online pharmacy sales., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The current study is aimed to introduce a wastewater-based epidemiology (WBE) approach for the first time on the African continent where substance abuse data is limited. The study included the quantification of several drugs of abuse (DOA) in raw wastewater samples. Quantification of urinary metabolites as drug target residues (DTR), as well as enantiomeric profiling of chiral DOA was performed to distinguish between consumption and direct disposal into sewage. Monitoring campaigns were undertaken at two South African wastewater treatment works (WWTWs) located within two provinces of the country. The presence of non-racemic 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine, as well as the metabolite of cocaine, benzoylecgonine (BEG), confirmed their consumption within the areas investigated. Enantiomeric profiling further pointed to the abuse of methamphetamine as the primary DOA with use estimates calculated between 181.9 and 1184.8mg·day -1 ·1000inhabitants -1 . Population-normalised mass loads for MDMA and cocaine confirmed their status as secondary DOA within the study sites. Use estimates for the new psychoactive substance (NPS) mephedrone were performed for one WWTW. The minor metabolite of heroin, O-6-monoacetylmorphine (O-6-MAM), was also detected at one WWTW and served as a qualitative indicator for heroin abuse within the area. These findings provide a novel comparison of the WBE approach in a developing-country with other global studies, with the aim to strengthen this approach as a tool to inform drug prevention strategies in countries where substance abuse data is limited due to financial constraints and lack of government structures to facilitate conventional monitoring., (Copyright © 2017. Published by Elsevier B.V.)

The aim of this paper is to present the first study on spatial and temporal variation in the enantiomeric profile of chiral drugs in eight European cities. Wastewater-based epidemiology (WBE) and enantioselective analysis were combined to evaluate trends in illicit drug use in the context of their consumption vs direct disposal as well as their synthetic production routes. Spatial variations in amphetamine loads were observed with higher use in Northern European cities. Enantioselective analysis showed a general enrichment of amphetamine with the R-(-)-enantiomer in wastewater indicating its abuse. High loads of racemic methamphetamine were detected in Oslo (EF = 0.49 ± 0.02). This is in contrast to other European cities where S-(+)-methamphetamine was the predominant enantiomer. This indicates different methods of methamphetamine synthesis and/or trafficking routes in Oslo, compared with the other cities tested. An enrichment of MDMA with the R-(-)-enantiomer was observed in European wastewaters indicating MDMA consumption rather than disposal of unused drug. MDA's chiral signature indicated its enrichment with the S-(+)-enantiomer, which confirms its origin from MDMA metabolism in humans. HMMA was also detected at quantifiable concentrations in wastewater and was found to be a suitable biomarker for MDMA consumption. Mephedrone was only detected in wastewater from the United Kingdom with population-normalised loads up to 47.7 mg 1000 people -1 day -1 . The enrichment of mephedrone in the R-(+)-enantiomer in wastewater suggests stereoselective metabolism in humans, hence consumption, rather than direct disposal of the drug. The investigation of drug precursors, such as ephedrine, showed that their presence was reasonably ascribed to their medical use., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared with the human urinary excretion profile. A good match was found for 1,7-dimethyluric acid, an exclusive caffeine metabolite, suggesting that might be a suitable biomarker in wastewater for assessing population-level caffeine consumption. A correction factor was developed considering the percentage of excretion of this metabolite in humans, according to published pharmacokinetic studies. Daily caffeine intake estimated from wastewater analysis was compared with the average daily intake calculated from the average amount of coffee consumed by country per capita. Good agreement was found in some cities but further information is needed to standardize this approach. Wastewater analysis proved useful to providing additional local information on caffeine use., (Copyright © 2017 Elsevier B.V. All rights reserved.)

European legislation focusing on water quality is expected to broaden to encompass several pharmaceuticals as priority hazardous substances. This manuscript aims to challenge current regulatory approaches that do not recognize stereochemistry of chiral pharmaceuticals by testing the hypothesis that environmental transformation and effects of chiral pharmaceuticals are stereoselective. Our experiments revealed that, while degradation of chiral fluoxetine (FL) in river water occurs via non-enantioselective photochemical and mildly-enantioselective microbial processes favoring the (R)-enantiomer, a pronounced enantioselectivity favoring (S)-FL (leading to the formation of (S)-NFL (norfluoxetine)) is observed during activated sludge treatment. Toxicity tests proved strong enantiomer-specific toxicity in the case of Tetrahymena thermophila, protozoa that are utilized during activated sludge treatment ((R)-FL is 30× more toxic than (S)-FL; (S)-NFL is 10× more toxic than (S)-FL). This is of paramount importance as preferential degradation of (S)-FL in activated sludge microcosms leads to the enrichment of FL with 30× more toxic (R)-FL and formation of 10× more toxic (S)-NFL. It is commonly assumed that a decreased concentration of FL leads to decreased biological impact. Our study proves that despite the overall decrease in FL concentration, accumulation of toxic (R)-FL and formation of toxic (S)-NFL leads to much higher than presumed toxicological effects.

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., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A large number of emerging contaminants (ECs) are known to persist in surface waters, and create pressure on wastewater treatment works (WWTW) for their effective removal. Although a large database for the levels of these pollutants in water systems exist globally, there is still a lack in the correlation of the levels of these pollutants with possible long-term adverse health effects in wildlife and humans, such as endocrine disruption. The current study detected a total of 55 ECs in WWTW influent surface water, 41 ECs in effluent, and 40 ECs in environmental waters located upstream and downstream of the plant. A list of ECs persisted through the WWTW process, with 28% of all detected ECs removed by less than 50%, and 18% of all ECs were removed by less than 25%. Negative mass balances of some pharmaceuticals and metabolites were observed within the WWTW, suggesting possible back-transformation of ECs during wastewater treatment. Three parental illicit drug compounds were detected within the influent of the WWTW, with concentrations ranging between 27.6 and 147.0 ng L -1 for cocaine, 35.6-120.6 ng L -1 for mephedrone, and 270.9-450.2 ng L -1 for methamphetamine. The related environmental risks are also discussed for some ECs, with particular reference to their ability to disrupt endocrine systems. The current study propose the potential of the pharmaceuticals carbamazepine, naproxen, diclofenac and ibuprofen to be regarded as priority ECs for environmental monitoring due to their regular detection and persistence in environmental waters and their possible contribution towards adverse health effects in humans and wildlife., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In constructed wetlands micropollutants can be removed from water by phytoremediation. However, micropollutant uptake and metabolism by plants here is poorly understood due to the lack of good analytical approaches. Reported herein is the first methodology developed and validated for the multi-residue determination of 81 micropollutants (pharmaceuticals, personal care products and illicit drugs) in the emergent macrophyte Phragmites australis. The method involved extraction by microwave accelerated extraction (MAE), clean-up using off-line solid phase extraction and analysis by ultra-high-performance liquid chromatography tandem mass spectrometry. Development of the MAE method found the influence of studied variables on micropollutant recovery to be: extraction temperature > sample mass > solvent composition. Validation of the developed extraction protocol revealed method recoveries were in the range 80-120% for the majority of micropollutants. Method quantitation limits (MQLs) were generally <5 ng g -1 dry weight demonstrating the sensitivity of the methodology. Application of the method to P. australis from a constructed wetland used to treat trickling filter effluent found 17 micropollutants above their MQL, up to concentrations of 200 ng g -1 . Other than uptake, the presence of several metabolites (carbamazepine 10,11 epoxide, desvenlafaxine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, N-desmethyltramadol and norketamine) indicated metabolism within the plant may also occur. This new analytical methodology will enable a process mass balance of the constructed wetland to be attained for the first time, and thus help understand the role of phytoremediation in micropollutant removal by such systems., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

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 α 1 -acid glycoprotein chiral stationary phase. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

The popularity of new psychoactive substances (NPS) has grown in recent years, with certain NPS commonly and preferentially consumed even following the introduction of preventative legislation. With the objective to improve the knowledge on the use of NPS, a rapid and very sensitive method was developed for the determination of ten priority NPS (N-ethylcathinone, methylenedioxypyrovalerone (MDPV), methylone, butylone, methedrone, mephedrone, naphyrone, 25-C-NBOMe, 25-I-NBOMe and 25-B-NBOMe) in influent wastewater. Sample clean-up and pre-concentration was made by off-line solid phase extraction (SPE) with Oasis MCX cartridges. Isotopically labelled internal standards were used to correct for matrix effects and potential SPE losses. Following chromatographic separation on a C 18 column within 6 min, the compounds were measured by tandem mass spectrometry in positive ionization mode. The method was optimised and validated for all compounds. Limits of quantification were evaluated by spiking influent wastewater samples at 1 or 5 ng/L. An investigation into the stability of these compounds in influent wastewater was also performed, showing that, following acidification at pH 2, all compounds were relatively stable for up to 7 days. The method was then applied to influent wastewater samples from eight European countries, in which mephedrone, methylone and MDPV were detected. This work reveals that although NPS use is not as extensive as for classic illicit drugs, the application of a highly sensitive analytical procedure makes their detection in wastewater possible. The developed analytical methodology forms the basis of a subsequent model-based back-calculation of abuse rate in urban areas (i.e. wastewater-based epidemiology)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Monitoring the scale of pharmaceuticals, illicit and licit drugs consumption is important to assess the needs of law enforcement and public health, and provides more information about the different trends within different countries. Community drug use patterns are usually described by national surveys, sales and seizure data. Wastewater-based epidemiology (WBE) has been shown to be a reliable approach complementing such surveys., Method: This study aims to compare and correlate the consumption estimates of pharmaceuticals, illicit drugs, alcohol, nicotine and caffeine from wastewater analysis and other sources of information. Wastewater samples were collected in 2015 from 8 different European cities over a one week period, representing a population of approximately 5 million people. Published pharmaceutical sale, illicit drug seizure and alcohol, tobacco and caffeine use data were used for the comparison., Results: High agreement was found between wastewater and other data sources for pharmaceuticals and cocaine, whereas amphetamines, alcohol and caffeine showed a moderate correlation. methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) and nicotine did not correlate with other sources of data. Most of the poor correlations were explained as part of the uncertainties related with the use estimates and were improved with other complementary sources of data., Conclusions: This work confirms the promising future of WBE as a complementary approach to obtain a more accurate picture of substance use situation within different communities. Our findings suggest further improvements to reduce the uncertainties associated with both sources of information in order to make the data more comparable.

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Intentional or accidental release (direct disposal) of high loads of unused pharmaceuticals into wastewater can go unnoticed. Here, direct disposal of a pharmaceutical drug via the sewer network was identified for the first time using wastewater analysis. An irregularly high load of the antidepressant fluoxetine in raw wastewater (10.5 ± 2.4 g d(-1)) was up to 11 times greater than any other day. National prescription data revealed a predicted daily fluoxetine load for the studied treatment works to be 0.4-1.6 g d(-1). Enantio-selective analysis showed the high load of fluoxetine was present as a racemic mixture, which is typical for fluoxetine in dispensed formulations. As fluoxetine undergoes stereoselective metabolism within the body, a racemic mixture in wastewater suggests a nonconsumed drug was the major contributor of the high load. This was confirmed by its major metabolite norfluoxetine whose load did not increase on this day. Considering the most commonly prescribed formulation of fluoxetine, this increased load accounts for the disposal of ∼915 capsules. Furthermore, as fluoxetine is prescribed as one capsule per day, disposal is unlikely to be at the patient level. It is postulated that direct disposal was from a facility which handles larger quantities of the drug (e.g., a pharmacy).

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: 1.7 ng L(-1) (metoprolol) - 1321 ng L(-1) (tramadol) in influent,

This review identifies understudied areas of emerging contaminant (EC) research in wastewaters and the environment, and recommends direction for future monitoring. Non-regulated trace organic ECs including pharmaceuticals, illicit drugs and personal care products are focused on due to ongoing policy initiatives and the expectant broadening of environmental legislation. These ECs are ubiquitous in the aquatic environment, mainly derived from the discharge of municipal wastewater effluents. Their presence is of concern due to the possible ecological impact (e.g., endocrine disruption) to biota within the environment. To better understand their fate in wastewaters and in the environment, a standardised approach to sampling is needed. This ensures representative data is attained and facilitates a better understanding of spatial and temporal trends of EC occurrence. During wastewater treatment, there is a lack of suspended particulate matter analysis due to further preparation requirements and a lack of good analytical approaches. This results in the under-reporting of several ECs entering wastewater treatment works (WwTWs) and the aquatic environment. Also, sludge can act as a concentrating medium for some chemicals during wastewater treatment. The majority of treated sludge is applied directly to agricultural land without analysis for ECs. As a result there is a paucity of information on the fate of ECs in soils and consequently, there has been no driver to investigate the toxicity to exposed terrestrial organisms. Therefore a more holistic approach to environmental monitoring is required, such that the fate and impact of ECs in all exposed environmental compartments are studied. The traditional analytical approach of applying targeted screening with low resolution mass spectrometry (e.g., triple quadrupoles) results in numerous chemicals such as transformation products going undetected. These can exhibit similar toxicity to the parent EC, demonstrating the necessity of using an integrated analytical approach which compliments targeted and non-targeted screening with biological assays to measure ecological impact. With respect to current toxicity testing protocols, failure to consider the enantiomeric distribution of chiral compounds found in the environment, and the possible toxicological differences between enantiomers is concerning. Such information is essential for the development of more accurate environmental risk assessment., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The enantiomeric and diastereomeric profiling of chiral pharmaceuticals (ephedrine, norephedrine, atenolol and venlafaxine) and illicit drugs (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA)) was undertaken over a period of fourteen consecutive days in three wastewater treatment plants (WWTPs) in the city of Valencia, Spain. Degradation efficiency of WWTPs was found to be compound and enantiomer dependent. Selective enantiomer enrichment was observed for several target analytes. Amphetamine and MDMA were enriched with R(-)-enantiomers. 1S,2S(+)-pseudoephedrine was found to be more readily degradable during activated sludge treatment than its diastereomer 1R,2S(-)-ephedrine. Atenolol underwent enrichment with either S(-)- or R(+)-enantiomer in different WWTPs. This unexpected enantiomeric variation in the stereoselective degradation of atenolol could be attributed to different processes utilized during activated sludge treatment. The application of (enantiomeric) profiling of wastewater revealed usage patterns of chiral drugs in the Valencia region., (Copyright © 2014. Published by Elsevier B.V.)

Analysis of wastewater with an aim of community-wide estimation of drug use is a new and very promising approach. Until now it was very difficult to determine if mass loads of studied drugs were actually originating from consumption, or disposal of unused drugs or production waste. This uncertainty in the estimation of community wide drugs use should not be underestimated. This paper aims to apply for the first time enantiomeric profiling in verifying sources of the presence of MDMA and amphetamine in wastewater based on a case study in two Dutch cities: Utrecht and Eindhoven. The results showed that MDMA is usually present in wastewater due to its consumption (MDMA enriched with R(-)-enantiomer). Excessively high mass loads of MDMA during a sampling campaign in Utrecht in 2011 proved to be racemic indicating direct disposal of unused MDMA possibly as a result of a police raid at a nearby illegal production facility. Enantiomeric profiling was also undertaken in order to verify the origin of unexpectedly high mass loads of amphetamine in the city of Eindhoven in 2011. Unfortunately, a distinction between consumption and direct disposal of unused amphetamine in Dutch wastewater could not be achieved. Further work will have to be undertaken to fully understand sources of amphetamine in Dutch wastewaters., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Illicit drug use is a global phenomenon involving millions of individuals, which results in serious health and social costs. The chemical analysis of urban wastewater for the excretion products of illicit drugs is a potent approach for monitoring patterns and trends of illicit drug use in a community. The first international and multidisciplinary conference on this topic was recently organized to present the epidemiological knowledge of patterns in drug use and the information obtained from wastewater analysis. This paper gives an overview of the main issues that emerged during the conference, focusing on the identified research gaps and requirements and on the future challenges and opportunities from bringing together wastewater analysis and drug epidemiology. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) uses an established multi-indicator system to monitor illicit drug use and to identify the emergence of new psychoactive substances. The methodological challenges of monitoring a hidden and stigmatized behavior like drug use include the limitations of self-report data and reporting delays. An increasing evidence base suggests that wastewater analysis can address some of these problems. Specifically this technique can: monitor temporal and spatial trends in drug use at different scales, provide updated estimates of drug use, and identify changing habits and the use of new substances. A best practice protocol developed by a Europe-wide network of experts is available to produce homogeneous and comparable data at different sites. The systematic evaluation of uncertainties related to wastewater analysis has highlighted which areas require careful control and those that need further investigation to generally improve the approach. Wastewater analysis has considerable potential to complement existing approaches for monitoring drug use due to its ability to produce objective, real-time estimates of drug use and to give timely information of any change in the patterns of use.

This paper presents, for the first time, community-wide estimation of drug and pharmaceuticals consumption in England using wastewater analysis and a large number of compounds. Among groups of compounds studied were: stimulants, hallucinogens and their metabolites, opioids, morphine derivatives, benzodiazepines, antidepressants and others. Obtained results showed the usefulness of wastewater analysis in order to provide estimates of local community drug consumption. It is noticeable that where target compounds could be compared to NHS prescription statistics, good comparisons were apparent between the two sets of data. These compounds include oxycodone, dihydrocodeine, methadone, tramadol, temazepam and diazepam. Whereas, discrepancies were observed for propoxyphene, codeine, dosulepin and venlafaxine (over-estimations in each case except codeine). Potential reasons for discrepancies include: sales of drugs sold without prescription and not included within NHS data, abuse of a drug with the compound trafficked through illegal sources, different consumption patterns in different areas, direct disposal leading to over estimations when using parent compound as the drug target residue and excretion factors not being representative of the local community. It is noticeable that using a metabolite (and not a parent drug) as a biomarker leads to higher certainty of obtained estimates. With regard to illicit drugs, consistent and logical results were reported. Monitoring of these compounds over a one week period highlighted the expected recreational use of many of these drugs (e.g. cocaine and MDMA) and the more consistent use of others (e.g. methadone)., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Concentrations of metabolites of illicit drugs in sewage water can be measured with great accuracy and precision, thanks to the development of sensitive and robust analytical methods. Based on assumptions about factors including the excretion profile of the parent drug, routes of administration and the number of individuals using the wastewater system, the level of consumption of a drug can be estimated from such measured concentrations. When presenting results from these 'back-calculations', the multiple sources of uncertainty are often discussed, but are not usually explicitly taken into account in the estimation process. In this paper we demonstrate how these calculations can be placed in a more formal statistical framework by assuming a distribution for each parameter involved, based on a review of the evidence underpinning it. Using a Monte Carlo simulations approach, it is then straightforward to propagate uncertainty in each parameter through the back-calculations, producing a distribution for instead of a single estimate of daily or average consumption. This can be summarised for example by a median and credible interval. To demonstrate this approach, we estimate cocaine consumption in a large urban UK population, using measured concentrations of two of its metabolites, benzoylecgonine and norbenzoylecgonine. We also demonstrate a more sophisticated analysis, implemented within a Bayesian statistical framework using Markov chain Monte Carlo simulation. Our model allows the two metabolites to simultaneously inform estimates of daily cocaine consumption and explicitly allows for variability between days. After accounting for this variability, the resulting credible interval for average daily consumption is appropriately wider, representing additional uncertainty. We discuss possibilities for extensions to the model, and whether analysis of wastewater samples has potential to contribute to a prevalence model for illicit drug use., (Copyright © 2014. Published by Elsevier B.V.)

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.

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., (Copyright © 2013 Elsevier B.V. All rights reserved.)