Search

Wastewater-based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population-normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011-17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data.Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017.Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries.Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of ΔBenzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North-Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge.The analysis of wastewater to quantify drug loads provides near real-time drug use estimates that globally correspond to prevalence and seizure data.

Graphical abstract, Pharmaceuticals, illicit drugs and personal care products are emerging contaminants widely distributed in water. Currently, a number of solid-phase extraction (SPE) procedures followed by liquid chromatography tandem mass spectrometry (LC–MS/MS) have been reported. However, target analysis of selected compounds is commonly used whereas other related contaminants present in the sample remain invisible. Carmona et al. [1] described a method for determining 21 emerging contaminants by LC–MS/MS with improved mobile phases. We tested this protocol in combination with high resolution mass spectrometry using a quadrupole time-of-flight (QqTOF) instrument to get a wide non-target screening approach in order to have a broader scope and more practical method for detecting licit and illicit drugs and personal care products than traditional target methods. The essential points in the method are: • The screening capabilities of QqTOF (ABSciex Triple TOF™) are used for detecting and identifying non-target pharmaceuticals and a large number of other emerging contaminants in water. • The quantitative features of the instrument, the Achilles heel of the QqTOF mass spectrometers, are established for few selected compounds. • The method may be applied to identify a large number of emerging contaminants in water. However, pre-validation will be needed to quantify them.

Thirty-seven laboratories from 25 countries present the development of an inter-laboratory testing scheme for the analysis of seven illicit drug residues in standard solutions, tap- and wastewater. Almost 10 000 concentration values were evaluated: triplicates of up to five samples and 26 laboratories per year. The setup was substantially improved with experiences gained across the six repetitions (e.g. matrix type, sample conditions, spiking levels). From this, (pre-)analytical issues (e.g. pH adjustment, filtration) were revealed for specific analytes which resulted in formulation of best-practice protocols for inter-laboratory setup and analytical procedures. The results illustrate the effectiveness of the inter-laboratory setup to assess laboratory performance in the framework of wastewater-based epidemiology. The exercise proved that measurements of laboratories were of high quality (>80% satisfactory results for six out of seven analytes) and that analytical follow-up is important to assist laboratories in improving robustness of wastewater-based epidemiology results., This article is based upon work from COST Action ES1307 supported by COST (European Cooperation in Science and Technology). We wish to acknowledge EMCDDA and Yeonsuk Ryu for support in the organization of the scheme and assistance in the preparation of the test samples, respectively. The following funding sources are acknowledged: the Research Foundation – Flanders (FWO) (Grant number: 1285216N), the Spanish Ministry of Economy, Industry and Competitiveness, the Generalitat Valenciana, Xunta de Galicia, Stavros Niarchos Foundation, Office for Combating Narcotic Drug Abuse of the Government of the Republic of Croatia, EU FP7 project SOLUTIONS (603437), the Government of Catalonia, the Natural Sciences and Engineering Research Council of Canada (NSERC), Ministry of Education, Youth and Sports of the Czech Republic (projects CENAKVA and CENAKVA II), EU Marie Skłodowska-Curie Fellowship (APOLLO 749845) and the Swiss National Science Foundation (SNSF, P2LAP2_164892). The following persons are acknowledged for help in sample analysis: Marijan Ahel, Evroula Hapeshi, Popi Karaolia, Esther López-García, Nicola Mastroianni, Cristina Postigo, Inés Racamonde, Rosario Rodil, Isaac Rodríguez, Tania Rodríguez-Álvarez, Ivan Senta, and Senka Terzic.

Wastewater-based epidemiology (WBE) started to develop significantly in the last 8 years due, in part, to the advance of liquid chromatography–mass spectrometry (LC–MS). Its initial objective ― to estimate the consumption of illicit drugs ― has been expanded to new psychoactive substances (NPS) and other human biomarkers of health, lifestyle and disease. The purpose of this review is to introduce recent methods and outstanding challenges in the application of LC–MS to these new targets, including target, suspect and non-target screening and, outline the workflows developed for discovering metabolites of NPS and biomarkers. Further, we discuss a number of specific methodological challenges that also deserve scrutiny in future research., This work has been supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and the ERDF (European Regional Development Fund) through the project Eco2TOOLS (CGL2015-64454-C2-1-R; http://www.eco2tools.es).

Drugs of abuse are continuously discharged into wastewaters as part of their elimination process. Pollution at very low concentrations appears to be broad in environmental compartments near populated areas. A total of 42 drugs of abuse and metabolites were analysed in surface water samples collected in 2012 and 2013 by solid phase extraction and liquid chromatography coupled to mass spectrometry. Analytical results of target compounds were georeferenced and integrated into a geographical information systems (GIS). Ecotoxicological risk of drugs of abuse detected in the Turia River was evaluated in this study by calculating risk quotient (RQ). In 2012, 6 compounds were detected in a total of 22 points. In 2013, 7 compounds were found in a total of 31 sampling sites, 4 of them also detected in 2012. The most frequent compound was benzoylecgonine, detected in 9 sampling points in 2012 and 8 in 2013, at an average concentration of 25.4 ng/L and 14.02 ng/L. Codeine reached the maximum concentration of detected compounds (101 ng/L) in 2013. GIS provided the spatial incidence of drugs of abuse along the Turia River basin. The distribution of these compounds in 2012 and 2013 shows that the highest concentrations and frequency of drugs of abuse run into places with the highest population density. The RQ obtained from measured concentrations of detected drugs predict that no short-term environmental risk might be expected. Further research including multi-stressors studies with more potentially persistent or pseudo-persistent organic pollutants in surface waters is needed to establish relationships with human pressure in a river basin., This work has been supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and the European Regional Development Fund (ERDF) through the project, Eco2TOOLS, http://www.eco2tools.es (Project Ref. CGL2015-64454-C2-1-R). M. Jesús Andrés-Costa also thanks the Spanish Ministry of Economy and Competitiveness for her FPI grant.

The occurrence of 8 drugs of abuse and metabolites in the influent and effluent of the 3 Wastewater Treatment Plants (WWTP) that treat wastewater from Valencia was studied in 2011, 2012 and 2013. Target drugs except 6-monoacetylmorphine (6-ACMOR) were detected in 100% of the influents. The WWTPs eliminate cocaine (COC), amphetamine (AMP), methamphetamine (MAMP) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH). Benzoylecgonine (BECG) was also efficiently eliminated (93-98%), whereas 3,4-methylenedioxymethamphetamine (MDMA) presented removal rates of 32-57% and ketamine (KET) was not eliminated. The most consumed illicit drugs, according to the estimated concentrations of each compound in the studied WWTPs, were cannabis and COC followed by KET, AMP, MAMP, MDMA and heroin. Environmental risk assessment was evaluated by calculating Risk Quotient (RQ). MDMA and KET could pose a medium risk and low risk, respectively, to the aquatic organisms. Although short-term environmental risk is not worrisome, long-term effects cannot be known exactly.

Emerging drugs of abuse, belonging to many different chemical classes, are attracting users with promises of “legal” highs and easy access via internet. Prevalence of their consumption and abuse through wastewater-based epidemiology can only be realized if a suitable analytical screening procedure exists to detect and quantify them in water. Solid-phase extraction and ultra-high performance liquid chromatography quadrupole time-of-flight-mass spectrometry (UHPLC–QqTOF–MS/MS) was applied for rapid suspect screening as well as for the quantitative determination of 42 illicit drugs and metabolites in water. Using this platform, we were able to identify amphetamines, tryptamines, piperazines, pyrrolidinophenones, arylcyclohexylamines, cocainics, opioids and cannabinoids. Additionally, paracetamol, carbamazepine, ibersartan, valsartan, sulfamethoxazole, terbumeton, diuron, etc. (including degradation products as 3-hydroxy carbamazepine or deethylterbuthylazine) were detected. This method encompasses easy sample preparation and rapid identification of psychoactive drugs against a database that cover more than 2000 compounds that ionized in positive mode, and possibility to identify metabolites and degradation products as well as unknown compounds. The method for river water, influent and effluents samples was fully validated for the target psychoactive substances including assessment of matrix effects (-88–67.8%), recovery (42–115%), precision (, This work has been supported by the Spanish Ministry of Economy and Competitiveness and the ERDF (European Regional Development Fund) through the project, GCL2015-64454-C2-1-R and the University of Valencia through the project (UV-INV-AE15-348995).

Wastewater can provide a wealth of epidemiologic data on common drugs consumed and on health and nutritional problems based on the biomarkers excreted into community sewage systems. One of the biggest uncertainties of these studies is the estimation of the number of inhabitants served by the treatment plants. Twelve human urine biomarkers —5-hydroxyindoleacetic acid (5-HIAA), acesulfame, atenolol, caffeine, carbamazepine, codeine, cotinine, creatinine, hydrochlorothiazide (HCTZ), naproxen, salicylic acid (SA) and hydroxycotinine (OHCOT)— were determined by liquid chromatography-tandem mass spectrometry (LC–MS/MS) to estimate population size. The results reveal that populations calculated from cotinine, 5-HIAA and caffeine are commonly in agreement with those calculated by the hydrochemical parameters. Creatinine is too unstable to be applicable. HCTZ, naproxen, codeine, OHCOT and carbamazepine, under or overestimate the population compared to the hydrochemical population estimates but showed constant results through the weekdays. The consumption of cannabis, cocaine, heroin and bufotenine in Valencia was estimated for a week using different population calculations., This work has been supported by the Spanish Ministry of Economy and Competitiveness and the ERDF (European Regional Development Fund) through the project CGL2015-64454-C2-1-R and the University of Valencia through the project UV-INV-AE15-348995. M. Jesús Andrés-Costa also thanks the Spanish Ministry of Economy and Competitiveness for her FPI grant.

Alcohol consumption has been increasing in the last years and it has become a sociological problem due its derived health and safety problems. Ethyl sulfate is a secondary metabolite of the alcohol degradation that is excreted through the urine (0.010-0.016%) after alcohol ingestion and it is quite stable in water. In this study, a new methodology to determine ethyl sulfate by ion-pair liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Different ion-pairs and additives were tested directly in the sample extracts or in the mobile phase. The best ion-pair was set up adding 0.5M of tributylamine and 0.1% of formic acid to the sample. The limit of quantification was 0.3μgL-1 and the intra-day and inter-day precision of the method were ≤2.8 and ≤3.0%, respectively. Good linearity (r2, This work has been supported by the Spanish Ministry of Economy and Competitiveness through the projects nos. CSD2009-00065 and GCL2011-29703-C02-02. M. Jesús Andrés-Costa also thanks the Spanish Ministry FPI grant.

An analytical method for determining traditional and emerging drugs of abuse in particulate matter, sewage sludge and sediment has been developed and validated. A total of 41 drugs of abuse and metabolites including cocainics, tryptamines, amphetamines, arylcyclohexylamines, cathinones, morphine derivatives, pyrrolidifenones derivatives, entactogens, piperazines and other psychostimulants were selected. Samples were ultrasound extracted with McIlvaine buffer and methanol, and the extracts were cleaned up by solid phase extraction (SPE) using Strata-X cartridges. Drugs were eluted using methanol and methanol-dichloromethane and determined by liquid chromatography tandem mass spectrometry. The optimum solid-liquid extraction (SLE) conditions were: weight 1g of sample and ultrasound assisted extraction (UAE) with 10mL of methanol-McIlvain buffer (1:1, v/v, pH 4.5) for 10min. Recoveries for all compounds were ≥50% in the three matrices with the exception of ephedrine (EPHE), 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), ecgonine methyester (ECME), heroin (HER), 3,4-methylendioxyamphetamine (MDA) and 4-acetoxy N,N'-dimethyltryptamine (4-AcO-DIPT) and methadone (MET). Data acquisition was done by selective reaction monitoring (SRM), and the two most abundant product ions were used for confirmation. Limits of detection were lower than 1.32ngg-1 dry weight (d.w.) and limits of quantification were between 0.12 and 3.96ngg-1 (d.w.). The method was applied to the analysis of particulate matter, where cocaine (COC), benzoylecgonine (BECG), ecgoninemethylester (ECME), cocaethylene (COCET), methadone (MET) and codeine (COD) were mostly detected. In the case of dehydrated sludge, opioids are at higher concentration than cocainics and some emerging drugs such as 4-methoxyamphetamine (PMA), ketamine (KET) and bufotenine (BUF) were detected. In sediment COC, 4-methoxyphencyclidine (4-MeO-PCP), MET and BECG were most relevant compounds. © 2015 Elsevier B.V., This work has been supported by the Spanish Ministry of Economy and Competitiveness through the projects (GCL2011-29703-C02-02). M. Jesús Andrés-Costa also thanks the Spanish Ministry for the FPI grant.

AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins (IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+ nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated. RESULTS: In patients with MHE, BF was increased in cerebellar hemisphere (P = 0.03) and vermis (P = 0.012) and reduced in occipital lobe (P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE (P = 0.02). Bimanual coordination was impaired in patients without MHE (P = 0.05) and much more in patients with MHE (P < 0.0001). Visuo-motor coordination was impaired only in patients with MHE (P < 0.0001). Attention was slightly affected in patients without MHE and more strongly in patients with MHE (P < 0.0001). BF in cerebellar hemisphere and vermis correlated with performance in most tests of PHES [(number connection tests A (NCT-A), B (NCT-B) and line tracing test] and in the congruent task of Stroop test. BF in frontal lobe correlated with NCT-A. Performance in bimanual and visuomotor coordination tests correlated only with BF in cerebellar hemisphere. BF in occipital lobe correlates with performance in the PHES battery and with CFF. BF in cerebellar hemisphere correlates with plasma cGMP and nitric oxide (NO) metabolites. BF in vermis cerebellar also correlates with NO metabolites and with 3-nitrotyrosine. IL-18 in plasma correlates with BF in thalamus and occipital lobe. CONCLUSION: Non invasive BF determination in cerebellum using ASL may detect MHE earlier than the PHES. Altered NO-cGMP pathway seems to be associated to altered BF in cerebellum. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.