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•Seasonal variation of pharmaceuticals present in a Spanish river was monitored.•Use of different MS instruments permitted comprehensive monitoring.•Four out of five antibiotics ...included in the EU Watch List were found.•Ecological risks were mainly driven by phenazone > azithromycin > diclofenac.•Severe ecological risks observed in 3 out of 19 sampling sites downstream of WWTPs.
Pharmaceuticals are biologically active molecules that may exert toxic effects to a wide range of aquatic organisms. They are considered contaminants of emerging concern due to their common presence in wastewaters and in the receiving surface waters, and the lack of specific regulations to monitor their environmental occurrence and risks. In this work, the environmental exposure and risks of pharmaceuticals have been studied in the Mijares River, Eastern Mediterranean coast (Spain). A total of 57 surface water samples from 19 sampling points were collected in three monitoring campaigns between June 2018 and February 2019. A list of 40 compounds was investigated using a quantitative target UHPLC-MS/MS method. In order to complement the data obtained, a wide-scope screening of pharmaceuticals and metabolites was also performed by UHPLC-HRMS. The ecological risks posed by the pharmaceutical mixtures were evaluated using species sensitivity distributions built with chronic toxicity data for aquatic organisms. In this study, up to 69 pharmaceuticals and 9 metabolites were identified, out of which 35 compounds were assessed using the quantitative method. The highest concentrations in water corresponded to acetaminophen, gabapentin, venlafaxine, valsartan, ciprofloxacin and diclofenac. The compounds that were found to exert the highest toxic pressure on the aquatic ecosystems were principally analgesic/anti-inflammatory drugs and antibiotics. These were: phenazone > azithromycin > diclofenac, and to a lower extent norfloxacin > ciprofloxacin > clarithromycin. The monitored pharmaceutical mixtures are expected to exert severe ecological risks in areas downstream of WWTP discharges, with the percentage of aquatic species affected ranging between 65% and 82% in 3 out of the 19 evaluated sites. In addition, five antibiotics were found to exceed antibiotic resistance thresholds, thus potentially contributing to resistance gene enrichment in environmental bacteria. This work illustrates the wide use and impact of pharmaceuticals in the area under study, and the vulnerability of surface waters if only conventional wastewater treatments are applied. Several compounds included in this study should be incorporated in future water monitoring programs to help in the development of future regulations, due to their potential risk to the aquatic environment.
The recent development of broad-scope high resolution mass spectrometry (HRMS) screening methods has resulted in a much improved capability for new compound identification in environmental samples. ...However, positive identifications at the ng/L concentration level rely on analytical reference standards for chromatographic retention time (tR) and mass spectral comparisons. Chromatographic tR prediction can play a role in increasing confidence in suspect screening efforts for new compounds in the environment, especially when standards are not available, but reliable methods are lacking. The current work focuses on the development of artificial neural networks (ANNs) for tR prediction in gradient reversed-phase liquid chromatography and applied along with HRMS data to suspect screening of wastewater and environmental surface water samples. Based on a compound tR dataset of >500 compounds, an optimized 4-layer back-propagation multi-layer perceptron model enabled predictions for 85% of all compounds to within 2min of their measured tR for training (n=344) and verification (n=100) datasets. To evaluate the ANN ability for generalization to new data, the model was further tested using 100 randomly selected compounds and revealed 95% prediction accuracy within the 2-minute elution interval. Given the increasing concern on the presence of drug metabolites and other transformation products (TPs) in the aquatic environment, the model was applied along with HRMS data for preliminary identification of pharmaceutically-related compounds in real samples. Examples of compounds where reference standards were subsequently acquired and later confirmed are also presented. To our knowledge, this work presents for the first time, the successful application of an accurate retention time predictor and HRMS data-mining using the largest number of compounds to preliminarily identify new or emerging contaminants in wastewater and surface waters.
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•A retention time predictor based on artificial neural networks is presented.•Using 550 compounds, 90% could be predicted within 2min.•A notable number of peaks (false positives) could be discarded for further research.•Useful in the tentative identification of metabolites and transformation products•This approach highly facilitates wide-scope screening of organic contaminants.
•Water quality was evaluated with a panel of health-relevant toxicity bioassays.•Indirect reuse of outlet wastewater did not affect drinking water quality negatively.•Wastewater treatment reduced ...most bioactivities as compared to incoming water.•Nrf2 activity was not markedly increased by chlorination of treated wastewater.•AhR activity increased in pipeline-system and after chlorination treatment.
Indirect potable reuse of wastewater is a practice that is gaining attention, aiming to increase freshwater supplies to meet water scarcity. However, reusing effluent wastewater for drinking water production comes with a paired risk of adverse health effects, due to the potential presence of pathogenic microorganisms and hazardous micropollutants. Disinfection is an established method to reduce microbial hazards in drinking water, but it has been associated with formation of disinfection by-products (DBPs). In this study, we performed an effect-based assessment of chemical hazards in a system wherein a full-scale trial of disinfection by chlorination, of the treated wastewater was performed prior discharge to the reciepient river. The presence of bioactive pollutants was assessed along the entire treatment system, starting from incoming wastewater to finished drinking water at seven sites in and around the Llobregat River in Barcelona, Spain. Samples were collected in two campaigns, with and without applied chlorination treatment (13 mg Cl2/L) to the effluent wastewater. The water samples were analysed for cell viability, oxidative stress response (Nrf2 activity), estrogenicity, androgenicity, aryl hydrocarbon receptor (AhR) activity and activation of NFĸB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling using stably transfected mammalian cell lines. Nrf2 activity, estrogen receptor activation and AhR activation was detected in all investigated samples. Overall, removal efficiencies were high in both wastewater treatment and drinking water treatment samples for most of the studied endpoints. No increase in oxidative stress (Nrf2 activity) could be attributed to the additional chlorination treatment of the effluent wastewater. However, we found an increase in AhR activity and a reduction of ER agonistic activity after chlorination treatment of effluent wastewater. The bioactivity detected in finished drinking water was considerably lower compared to what was found in effluent wastewater. We could thus conclude that indirect reuse of treated wastewater for drinking water production can be possible without compromising drinking water quality. This study contributed important knowledge in efforts to increase the reuse of treated wastewater as a source for drinking water production.
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The information obtained from the chemical analysis of specific human excretion products (biomarkers) in urban wastewater can be used to estimate the exposure or consumption of the population under ...investigation to a defined substance. A proper biomarker can provide relevant information about lifestyle habits, health and wellbeing, but its selection is not an easy task as it should fulfil several specific requirements in order to be successfully employed. This paper aims to summarize the current knowledge related to the most relevant biomarkers used so far. In addition, some potential wastewater biomarkers that could be used for future applications were evaluated. For this purpose, representative chemical classes have been chosen and grouped in four main categories: (i) those that provide estimates of lifestyle factors and substance use, (ii) those used to estimate the exposure to toxicants present in the environment and food, (iii) those that have the potential to provide information about public health and illness and (iv) those used to estimate the population size. To facilitate the evaluation of the eligibility of a compound as a biomarker, information, when available, on stability in urine and wastewater and pharmacokinetic data (i.e. metabolism and urinary excretion profile) has been reviewed. Finally, several needs and recommendations for future research are proposed.
•Wastewater biomarkers provide information on lifestyle habits, health and wellbeing.•Specific criteria should be followed to select a suitable biomarker.•Report of the current knowledge of the most relevant biomarkers used so far•Proposal of potential wastewater biomarkers for future applications•Review of pharmacokinetic data and stability in urine and wastewater for each biomarker
Aims
To perform wastewater analyses to assess spatial differences and temporal changes of illicit drug use in a large European population.
Design
Analyses of raw wastewater over a 1‐week period in ...2012 and 2013.
Setting and Participants
Catchment areas of wastewater treatment plants (WWTPs) across Europe, as follows: 2012: 25 WWTPs in 11 countries (23 cities, total population 11.50 million); 2013: 47 WWTPs in 21 countries (42 cities, total population 24.74 million).
Measurements
Excretion products of five illicit drugs (cocaine, amphetamine, ecstasy, methamphetamine, cannabis) were quantified in wastewater samples using methods based on liquid chromatography coupled to mass spectrometry.
Findings
Spatial differences were assessed and confirmed to vary greatly across European metropolitan areas. In general, results were in agreement with traditional surveillance data, where available. While temporal changes were substantial in individual cities and years (P ranging from insignificant to <10−3), overall means were relatively stable. The overall mean of methamphetamine was an exception (apparent decline in 2012), as it was influenced mainly by four cities.
Conclusions
Wastewater analysis performed across Europe provides complementary evidence on illicit drug consumption and generally concurs with traditional surveillance data. Wastewater analysis can measure total illicit drug use more quickly and regularly than is the current norm for national surveys, and creates estimates where such data does not exist.
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► A methodology was developed for the determination of 24 drugs of abuse in sewage waters. ► Quantitative analyses were performed using liquid chromatography–HR Orbitrap mass ...spectrometer. ► Compared to QqQ results, Orbitrap is almost equally sensitive. ► Accurate mass full scan data allowed retrospective analysis.
This work illustrates the potential of liquid chromatography coupled to a hybrid linear ion trap Fourier Transform Orbitrap mass spectrometer for the simultaneous identification and quantification of 24 drugs of abuse and relevant metabolites in sewage water. The developed methodology consisted of automatic solid-phase extraction using Oasis HLB cartridges, chromatographic separation of the targeted drugs, full-scan accurate mass data acquisition under positive electrospray ionization mode over an m/z range of 50–600Da at a resolution of 30,000 FWHM and simultaneous MSn measurements to obtain information of fragment ions generated in the linear ion trap. Accurate mass of the protonated molecule, together with at least one nominal mass product ion and retention time allowed the confident identification of the compounds detected in these complex matrices. In addition to the highly reliable qualitative analysis, Orbitrap analyzer also proved to have satisfactory potential for quantification at sub-ppb analyte levels, a possibility that has been very little explored in the literature until now. The limits of quantification ranged from 4 to 68ngL−1 in influent sewage water, and from 2 to 35ngL−1 in effluent, with the exception of MDA, morphine and THC that presented higher values as a consequence of the high ionization suppression in this type of samples. Satisfactory recoveries (70–120%) and precision (<30%) for the overall procedure were obtained for all compounds with the exception of meta-chlorophenylpiperazine, methylphenidate and ketamine. Isotope-labelled internal standards were added to sewage samples as surrogates in order to correct for matrix effects and also for possible losses during sample treatment. The methodology developed was applied to sewage water samples from the Netherlands (influent and effluent), and the results were compared with those obtained by LC–MS/MS with triple quadrupole. Several drugs of abuse could be identified and quantified, mainly MDMA, benzoylecgonine, codeine, oxazepam and temazepam. Orbitrap also showed potential for retrospective investigation of ketamine metabolites in the samples without the need of additional analysis.
•Wastewater analysis provided insights on drug use during the SARS-CoV-2 pandemic.•Speculated decrease in consumption did not occur in all cities nor for all drugs.•Measures had different effects, ...even at the regional level.•Additional and complementary data needed to fully understand the impact on drug use.
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-Δ9-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.
The existence of pharmaceuticals and illicit drugs (PIDs) in environmental waters has led many analytical chemists to develop screening methods for monitoring purposes. Water samples can contain a ...huge number of possible contaminants, commonly at low concentrations, which makes their detection and identification problematic. Liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) has proven itself effective in the screening of environmental contaminants. The present work investigates the use of the most popular HRMS instruments, quadrupole time-of-flight and linear trap quadrupole-Orbitrap, from two different laboratories. A suspect screening for PIDs was carried out on wastewater (influent and effluent) and surface water samples from Castellón, Eastern Spain, and Cremona, Northern Italy, incorporating a database of 107 PIDs (including 220 fragment ions). A comparison between the findings of both instruments and of the samples was made which highlights the advantages and drawbacks of the strategies applied in each case. In total, 28 compounds were detected and/or identified by either/both instruments with irbesartan, valsartan, benzoylecgonine and caffeine being the most commonly found compounds across all samples.
Wastewater-based epidemiology (WBE) relies on the principle that traces of compounds, which a population is exposed to or consume, are excreted unchanged or as metabolites in urine and/or feces, and ...ultimately end up in the sewer network. Measuring target metabolic residues i.e. biomarkers in raw urban wastewater allows identifying the exposure or use of substances of interest in a community. Up to date, the most popular application of WBE is the estimation of illicit drug use and studies have been made mainly across Europe, which has allowed estimating and comparing drug use in many European cities. However, until now a comprehensive study applying WBE on the most frequently consumed illicit drugs has not been performed in South American countries. In this work, we applied this approach to samples from Colombia, selecting two of the most populated cities: Bogotá and Medellin. Several biomarkers were selected to estimate drug use of cocaine, cannabis, amphetamine, methamphetamine, MDMA (ecstasy), heroin and ketamine. Composite samples (24-h) were collected at the corresponding municipal wastewater treatment plants. Sample treatment was performed at location by applying solid-phase extraction (SPE). Before SPE, the samples were spiked with appropriate isotope labeled internal standards. In parallel, samples (spiked with the analytes under study at two concentration levels) were also processed for quality control. Analysis of influent wastewater was made by liquid chromatography-tandem mass spectrometry, with triple quadrupole analyzer. Data shown in this paper reveal a high use of cocaine by the population of the selected Colombian cities, particularly from Medellin, while the use of other illicit drugs were low. The relevance of using quality control samples, particularly in collaborative studies, as those presented in this work, where research groups from different countries participate and where the samples had to be shipped overseas, is highlighted in this paper.
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•Wastewater-based epidemiology was applied for the first time in Colombia.•Inclusion of control samples, previous to shipment, assures the quality of the data.•Emphasis was made on evaluating uncertainties associated with this study.•Cocaine was the most consumed illicit drug, particularly in Medellin.
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•Complex environmental samples screened with IM-HRMS using MetFrag and PubChemLite.•Mobility alignment improves spectrum quality and peak annotation.•Thirty-two compounds tentatively ...identified using suspect and non-target screening.•Predicted CCS values are valuable, automated implementation is not (yet) advised.•Non-target screening in complex samples remains a major challenge.
Identification of bioaccumulating contaminants of emerging concern (CECs) via suspect and non-target screening remains a challenging task. In this study, ion mobility separation with high-resolution mass spectrometry (IM-HRMS) was used to investigate the effects of drift time (DT) alignment on spectrum quality and peak annotation for screening of CECs in complex sample matrices using data independent acquisition (DIA). Data treatment approaches (Binary Sample Comparison) and prioritisation strategies (Halogen Match, co-occurrence of features in biota and the water phase) were explored in a case study on zebra mussel (Dreissena polymorpha) in Lake Mälaren, Sweden’s largest drinking water reservoir. DT alignment evidently improved the fragment spectrum quality by increasing the similarity score to reference spectra from on average (±standard deviation) 0.33 ± 0.31 to 0.64 ± 0.30 points, thus positively influencing structure elucidation efforts. Thirty-two features were tentatively identified at confidence level 3 or higher using MetFrag coupled with the new PubChemLite database, which included predicted collision cross-section values from CCSbase. The implementation of predicted mobility data was found to support compound annotation. This study illustrates a quantitative assessment of the benefits of IM-HRMS on spectral quality, which will enhance the performance of future screening studies of CECs in complex environmental matrices.
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