Publications by authors named "Juliet Kinyua"

24 Publications

  • Page 1 of 1

Investigation of Biotransformation Products of -Methoxymethylamphetamine and Dihydromephedrone in Wastewater by High-Resolution Mass Spectrometry.

Metabolites 2021 Jan 25;11(2). Epub 2021 Jan 25.

Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.

There is a paucity of information on biotransformation and stability of new psychoactive substances (NPS) in wastewater. Moreover, the fate of NPS and their transformation products (TPs) in wastewater treatment plants is not well understood. In this study, batch reactors seeded with activated sludge were set up to evaluate biotic, abiotic, and sorption losses of -methoxymethylamphetamine (PMMA) and dihydromephedrone (DHM) and identify TPs formed during these processes. Detection and identification of all compounds was performed with target and suspect screening approaches using liquid chromatography quadrupole-time-of-flight mass spectrometry. Influent and effluent 24 h composite wastewater samples were collected from Athens from 2014 to 2020. High elimination rates were found for PMMA (80%) and DHM (97%) after a seven-day experiment and degradation appeared to be related to biological activity in the active bioreactor. Ten TPs were identified and the main reactions were - and -demethylation, oxidation, and hydroxylation. Some TPs were reported for the first time and some were confirmed by reference standards. Identification of some TPs was enhanced by the use of an in-house retention time prediction model. Mephedrone and some of its previously reported human metabolites were formed from DHM incubation. Retrospective analysis showed that PMMA was the most frequently detected compound.
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http://dx.doi.org/10.3390/metabo11020066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912097PMC
January 2021

A Case Series of Etizolam in Opioid Related Deaths.

J Anal Toxicol 2020 Oct 8. Epub 2020 Oct 8.

Office of the Chief Medical Examiner, San Francisco, California, USA.

Etizolam is a novel psychoactive substance and novel benzodiazepine of the thienotriazolodiazepine class that has recently seen an increasing trend in use worldwide. We report a case series of 10 decedents with etizolam and opioids in their systems. The death investigation, expanded toxicology and medical investigation information were included for contextualization of etizolam in death. Etizolam was detected and confirmed within peripheral and cardiac blood, urine, vitreous humor and, in one case, gastric fluid by LC-MS-MS and LC-QTOF-MS methodologies. Death investigation indicated non-medical use of drugs. Medical investigation commonly noted pulmonary edema, cardiomegaly and cerebral swelling. The majority of the decedents appeared to unaware of the presence of etizolam and succumbed to the mixed drug toxicity of their routine depressant and narcotic analgesic drug of abuse in combination with etizolam. Etizolam use continues to be observed and poses as a potentially lethal contribution to multiple drug toxicity, especially in the age of the opioid crisis. Assessment of analytes like etizolam require up-to-date methodologies and vigilance in testing to better characterize the toxicology and interpret the contribution to death.
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http://dx.doi.org/10.1093/jat/bkaa146DOI Listing
October 2020

Investigating in-sewer transformation products formed from synthetic cathinones and phenethylamines using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Sci Total Environ 2018 Sep 6;634:331-340. Epub 2018 Apr 6.

Toxicological Center, Department of Pharmaceutical Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.

Recent studies have demonstrated the role of biofilms on the stability of drug residues in wastewater. These factors are pertinent in wastewater-based epidemiology (WBE) when estimating community-level drug use. However, there is scarce information on the biotransformation of drug residues in the presence of biofilms and the potential use of transformation products (TPs) as biomarkers in WBE. The purpose of this work was to investigate the formation of TPs in sewage reactors in the presence of biofilm mimicking conditions during in-sewer transport. Synthetic cathinones (methylenedioxypyrovalerone, methylone, mephedrone) and phenethylamines (4-methoxy-methamphetamine and 4-methoxyamphetamine) were incubated in individual reactors over a 24h period. Analysis of parent species and TPs was carried out using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QToFMS). Identification of TPs was done using suspect and non-target workflows. In total, 18 TPs were detected and identified with reduction of β-keto group, demethylenation, demethylation, and hydroxylation reactions observed for the synthetic cathinones. For the phenethylamines, N- and O-demethylation reactions were identified. Overall, the experiments showed varying stability for the parent species in wastewater in the presence of biofilms. The newly identified isomeric forms of TPs particularly for methylone and mephedrone can be used as potential target biomarkers for WBE studies due to their specificity and detectability within a 24h residence time.
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http://dx.doi.org/10.1016/j.scitotenv.2018.03.253DOI Listing
September 2018

Comparison of phosphodiesterase type V inhibitors use in eight European cities through analysis of urban wastewater.

Environ Int 2018 06 3;115:279-284. Epub 2018 Apr 3.

KWR Watercycle Research Institute, Chemical Water Quality and Health, P.O. Box 1072, 3430 BB Nieuwegein, The Netherlands; Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, P.O. Box 94248, 1090 GE Amsterdam, The Netherlands. Electronic address:

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. 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.
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http://dx.doi.org/10.1016/j.envint.2018.03.039DOI Listing
June 2018

Enantiomeric profiling of chiral illicit drugs in a pan-European study.

Water Res 2018 03 1;130:151-160. Epub 2017 Dec 1.

Department of Chemistry, Faculty of Science, University of Bath, Bath, BA2 7AY, UK. Electronic address:

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 day. 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.
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http://dx.doi.org/10.1016/j.watres.2017.11.051DOI Listing
March 2018

Estimation of caffeine intake from analysis of caffeine metabolites in wastewater.

Sci Total Environ 2017 Dec 8;609:1582-1588. Epub 2017 Aug 8.

IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Department of Environmental Health Sciences, Via La Masa 19, 20156 Milan, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.scitotenv.2017.07.258DOI Listing
December 2017

Qualitative screening for new psychoactive substances in wastewater collected during a city festival using liquid chromatography coupled to high-resolution mass spectrometry.

Chemosphere 2017 Oct 26;184:1186-1193. Epub 2017 Jun 26.

KWR Watercycle Research Institute, Chemical Water Quality and Health, P.O. Box 1072, 3430 BB, Nieuwegein, The Netherlands; Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, P.O. Box 94248, 1090 GE, Amsterdam, The Netherlands. Electronic address:

The inclusion of new psychoactive substances (NPS) in the wastewater-based epidemiology approach presents challenges, such as the reduced number of users that translates into low concentrations of residues and the limited pharmacokinetics information available, which renders the choice of target biomarker difficult. The sampling during special social settings, the analysis with improved analytical techniques, and data processing with specific workflow to narrow the search, are required approaches for a successful monitoring. This work presents the application of a qualitative screening technique to wastewater samples collected during a city festival, where likely users of recreational substances gather and consequently higher residual concentrations of used NPS are expected. The analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. Data were processed using an algorithm that involves the extraction of accurate masses (calculated based on molecular formula) of expected m/z from an in-house database containing about 2,000 entries, including NPS and transformation products. We positively identified eight NPS belonging to the classes of synthetic cathinones, phenethylamines and opioids. In addition, the presence of benzodiazepine analogues, classical drugs and other licit substances with potential for abuse was confirmed. The screening workflow based on a database search was useful in the identification of NPS biomarkers in wastewater. The findings highlight the specific classical drugs and low NPS use in the Netherlands. Additionally, meta-chlorophenylpiperazine (mCPP), 2,5-dimethoxy-4-bromophenethylamine (2C-B), and 4-fluoroamphetamine (FA) were identified in wastewater for the first time.
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http://dx.doi.org/10.1016/j.chemosphere.2017.06.101DOI Listing
October 2017

Wastewater-based epidemiology to assess pan-European pesticide exposure.

Water Res 2017 09 21;121:270-279. Epub 2017 May 21.

IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Department of Environmental Health Sciences, Via La Masa 19, 20156, Milan, Italy. Electronic address:

Human biomonitoring, i.e. the determination of chemicals and/or their metabolites in human specimens, is the most common and potent tool for assessing human exposure to pesticides, but it suffers from limitations such as high costs and biases in sampling. Wastewater-based epidemiology (WBE) is an innovative approach based on the chemical analysis of specific human metabolic excretion products (biomarkers) in wastewater, and provides objective and real-time information on xenobiotics directly or indirectly ingested by a population. This study applied the WBE approach for the first time to evaluate human exposure to pesticides in eight cities across Europe. 24 h-composite wastewater samples were collected from the main wastewater treatment plants and analyzed for urinary metabolites of three classes of pesticides, namely triazines, organophosphates and pyrethroids, by liquid chromatography-tandem mass spectrometry. The mass loads (mg/day/1000 inhabitants) were highest for organophosphates and lowest for triazines. Different patterns were observed among the cities and for the various classes of pesticides. Population weighted loads of specific biomarkers indicated higher exposure in Castellon, Milan, Copenhagen and Bristol for pyrethroids, and in Castellon, Bristol and Zurich for organophosphates. The lowest mass loads (mg/day/1000 inhabitants) were found in Utrecht and Oslo. These results were in agreement with several national statistics related to pesticides exposure such as pesticides sales. The daily intake of pyrethroids was estimated in each city and it was found to exceed the acceptable daily intake (ADI) only in one city (Castellon, Spain). This was the first large-scale application of WBE to monitor population exposure to pesticides. The results indicated that WBE can give new information about the "average exposure" of the population to pesticides, and is a useful complementary biomonitoring tool to study population-wide exposure to pesticides.
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http://dx.doi.org/10.1016/j.watres.2017.05.044DOI Listing
September 2017

Measuring biomarkers in wastewater as a new source of epidemiological information: Current state and future perspectives.

Environ Int 2017 Feb 27;99:131-150. Epub 2016 Dec 27.

Research Institute for Pesticides and Water, Universitat Jaume I, Castellon, Spain. Electronic address:

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.
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http://dx.doi.org/10.1016/j.envint.2016.12.016DOI Listing
February 2017

Increased levels of the oxidative stress biomarker 8-iso-prostaglandin F in wastewater associated with tobacco use.

Sci Rep 2016 12 15;6:39055. Epub 2016 Dec 15.

Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, NO-0349 Oslo, Norway.

Wastewater analysis has been demonstrated to be a complementary approach for assessing the overall patterns of drug use by a population while the full potential of wastewater-based epidemiology has yet to be explored. F-isoprostanes are a prototype wastewater biomarker to study the cumulative oxidative stress at a community level. In this work, 8-iso-prostaglandin F (8-iso-PGF) was analysed in raw 24 h-composite wastewater samples collected from 4 Norwegian and 7 other European cities in 2014 and 2015. Using the same samples, biomarkers of alcohol (ethyl sulfate) and tobacco (trans-3'-hydroxycotinine) use were also analysed to investigate any possible correlation between 8-iso-PGF and the consumption of the two drugs. The estimated per capita daily loads of 8-iso-PGF in the 11 cities ranged between 2.5 and 9.9 mg/day/1000 inhabitants with a population-weighted mean of 4.8 mg/day/1000 inhabitants. There were no temporal trends observed in the levels of 8-iso-PGF, however, spatial differences were found at the inter-city level correlating to the degree of urbanisation. The 8-iso-PGF mass load was found to be strongly associated with that of trans-3'-hydroxycotinine while it showed no correlation with ethyl sulfate. The present study shows the potential for 8-iso-PGF as a wastewater biomarker for the assessment of community public health.
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http://dx.doi.org/10.1038/srep39055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5157025PMC
December 2016

Liquid chromatography-tandem mass spectrometry determination of synthetic cathinones and phenethylamines in influent wastewater of eight European cities.

Chemosphere 2017 Feb 1;168:1032-1041. Epub 2016 Nov 1.

Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellón, Spain. Electronic address:

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 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).
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http://dx.doi.org/10.1016/j.chemosphere.2016.10.107DOI Listing
February 2017

Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities.

BMC Public Health 2016 10 1;16(1):1035. Epub 2016 Oct 1.

Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, Oslo, NO-0349, Norway.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045646PMC
http://dx.doi.org/10.1186/s12889-016-3686-5DOI Listing
October 2016

Qualitative screening of new psychoactive substances in pooled urine samples from Belgium and United Kingdom.

Sci Total Environ 2016 Dec 26;573:1527-1535. Epub 2016 Aug 26.

Toxicological Center, Department of Pharmaceutical Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address:

Concerns about new psychoactive substances (NPS) are increasing due to the rising frequency of serious intoxications. Analysis of biological fluids (urine) is necessary to get reliable information about the use of these substances. However, it is a challenging task due to the lack of analytical standards and the dynamic character of the NPS market. In the present work, a qualitative screening of NPS was carried out in 23 pooled urine samples collected from a city center in the UK and festivals in the UK and Belgium. The analytical method was based on data-independent acquisition mode using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. An in-house library was used with >1500 entries corresponding to NPS, classical drugs and metabolites. All samples contained 53 and 28 compounds of interest from the UK and Belgium respectively. Of the different compounds detected, about 70% were confirmed using retention time and product ions while the remaining compounds were identified using elucidated fragmentation pathways. The highest numbers of NPS identified in both countries were from the cathinone and phenylethylamine families, with a higher number being detected in samples from the festival in the UK. Moreover, several cathinone metabolites in human urine were detected and identified. The screening method proved useful to detect a large number of compounds and determine the use of NPS.
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http://dx.doi.org/10.1016/j.scitotenv.2016.08.124DOI Listing
December 2016

Profiles and changes in stimulant use in Belgium in the period of 2011-2015.

Sci Total Environ 2016 Sep 29;565:1011-1019. Epub 2016 May 29.

Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp (UA), Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address:

Adapting illicit drug policy strategies requires detailed knowledge on types and amounts of substances consumed by the target population. In this study, we applied wastewater-based epidemiology to detect spatio-temporal changes in the relative amounts of stimulants (amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), cocaine) used in seven locations in Belgium over 2011-2015. Clear geographical differences were observed with stimulant users in large cities (Antwerp, Brussels) showing a preference for cocaine, while amphetamine use was most abundant in smaller cities (Geraardsbergen, Koksijde, Lier, Ninove, Ostend). Results obtained across õdifferent years revealed that the investigated substances had a stable share in the total amount of stimulants used, suggesting that habits of stimulant use remained constant, although differences in absolute amounts were observed across years. Investigation of the weekly pattern in stimulant use showed an increase in the use of MDMA on the weekends compared to cocaine and amphetamine.
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http://dx.doi.org/10.1016/j.scitotenv.2016.05.128DOI Listing
September 2016

Drugs of abuse and alcohol consumption among different groups of population on the Greek Island of Lesvos through sewage-based epidemiology.

Sci Total Environ 2016 Sep 25;563-564:633-40. Epub 2016 May 25.

Department of Environment, University of the Aegean, University Hill, Mytilene 81 100, Greece.

The occurrence of 22 drugs of abuse, their metabolites, and the alcohol metabolite ethyl sulphate was investigated in raw sewage samples collected during the non-touristic season from three sewage treatment plants (STPs), which serve different sizes and types of population in the Greek island of Lesvos. Using the sewage-based epidemiology approach, the consumption of these substances was estimated. Five target analytes, cocaine (COC), benzoylecgonine (BE), 3,4-methylenedioxymethamphetamine (MDMA), 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) and ethyl sulphate (EtS) were detected at concentrations above their limit of quantification, whereas the rest eighteen target compounds were not detected. THC-COOH was detected in most of the samples with concentrations ranging between <20 and 90ngL(-1), followed by EtS (range <1700-12,243ngL(-1)). COC, BE, and MDMA were present only in the STP that serves Mytilene (the main city of the island), at mean concentrations of 3.9ngL(-1) for COC (95% CI: 1.7-6.1), 9.4ngL(-1) for BE (95% CI: -1.6-23) and 3.2ngL(-1) for MDMA (95% CI: 1.2-5.1). Back-calculations to an amount of used substance indicated more intense use of drugs among city population than rural and University population with average values of 9.5 and 1.2mgday(-1) per 1000 inhabitants for COC (95% CI: -1.43-20.4) and MDMA (95% CI: 0.52-1.85), respectively, and 2.8gday(-1) per 1000 inhabitants for tetrahydrocannabinol (THC) (95% CI: 2.4-3.1), the active ingredient of cannabis. Alcohol consumption was observed to be higher in the city population (5.4mL pure alcohol per day per inhabitant) than in the rural population (3.4mL pure alcohol per day per inhabitant), but the difference was not statistically significant. Consumption of THC differed significantly among the three STPs.
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http://dx.doi.org/10.1016/j.scitotenv.2016.04.130DOI Listing
September 2016

Identification of in vitro and in vivo human metabolites of the new psychoactive substance nitracaine by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Anal Bioanal Chem 2016 Jul 16;408(19):5221-9. Epub 2016 May 16.

Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk-Antwerp, Belgium.

The purpose of this work was to investigate the in vitro metabolism of nitracaine, a new psychoactive substance, using human liver microsome incubations, to evaluate the cytochrome P450 (CYP) enzyme isoforms responsible for the phase-I metabolism and to compare the information from the in vitro experiments with data resulting from an authentic user's urine sample. Accurate mass spectra of metabolites were obtained using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and were used in the structural identification of metabolites. Two major and three minor phase-I metabolites were identified from the in vitro experiments. The observed phase-I metabolites were formed through N-deethylation, N,N-deethylation, N-hydroxylation, and de-esterification, with CYP2B6 and CYP2C19 being the main enzymes catalyzing their formation. One glucuronidated product was identified in the phase-II metabolism experiments. All of these metabolites are reported for the first time in this study except the N-deethylation product. All the in vitro metabolites except the minor N,N-deethylation product were also present in the human urine sample, thus demonstrating the reliability of the in vitro experiments in the prediction of the in vivo metabolism of nitracaine. In addition to the metabolites, three transformation products (p-nitrobenzoic acid, p-aminobenzoic acid, and 3-(diethylamino)-2,2-dimethylpropan-1-ol) were identified, as well as several glucuronides and glutamine derived of them.
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http://dx.doi.org/10.1007/s00216-016-9616-7DOI Listing
July 2016

Screening for illicit drugs in pooled human urine and urinated soil samples and studies on the stability of urinary excretion products of cocaine, MDMA, and MDEA in wastewater by hyphenated mass spectrometry techniques.

Drug Test Anal 2017 Jan 17;9(1):106-114. Epub 2016 Feb 17.

Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg, Germany.

Monitoring population drug use through wastewater-based epidemiology (WBE) is a useful method to quantitatively follow trends and estimate total drug consumption in communities. Concentrations of drug biomarkers might be low in wastewater due to dilution; and therefore analysis of pooled urine (PU) is useful to detect consumed drugs and identify targets of illicit drugs use. The aims of the study were (1) to screen PU and urinated soil (US) samples collected at festivals for illicit drug excretion products using hyphenated techniques; (2) to develop and validate a hydrophilic interaction liquid chromatography - mass spectrometry / mass spectrometry (HILIC-MS/MS) method of quantifying urinary targets of identified drugs in wastewater; and (3) to conduct a 24 h stability study, using PU and US to better reflect the chemical environment for targets in wastewater. Cocaine (COC) and ecstasy-like compounds were the most frequently detected illicit drugs; an analytical method was developed to quantify their excretion products. Hydroxymethoxymethamphetamine (HMMA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), HMMA sulfate (HMMA-S), benzoylecgonine (BE), and cocaethylene (CE) had 85-102% of initial concentration after 8 h of incubation, whereas COC and ecgonine methyl ester (EME) had 74 and 67% after 8 h, respectively. HMMA showed a net increase during 24 h of incubation (107% ± 27, n = 8), possibly due to the cleavage of HMMA conjugates, and biotransformation of MDMA. The results suggest HMMA as analytical target for MDMA consumption in WBE, due to its stability in wastewater and its excretion as the main phase I metabolite of MDMA. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/dta.1957DOI Listing
January 2017

Spatial and temporal trends in alcohol consumption in Belgian cities: A wastewater-based approach.

Drug Alcohol Depend 2016 Mar 14;160:170-6. Epub 2016 Jan 14.

Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp (UA), Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address:

Background: In recent years, scientific evidence has emerged that wastewater-based epidemiology can deliver complementary information concerning the use of different substances of abuse. In this study, the potential of wastewater-based epidemiology in monitoring spatial and temporal trends in alcohol consumption in different populations in Belgium has been examined.

Methods: Concentrations of ethyl sulphate, a minor Phase-II metabolite of ethanol, in 163 influent wastewater samples from eight wastewater treatment plants in Belgium in the period 2013-2015 were measured with liquid chromatography coupled to tandem mass spectrometry and used to estimate alcohol consumption.

Results: The highest levels of alcohol consumption were detected in the metropoles Antwerp and Brussels compared to smaller villages. Annual variations were detected, with a higher alcohol consumption measured in 2013 compared with 2014. The weekly pattern showed a clear week and weekend difference in alcohol use, with intermediate levels on Monday and Friday. The results were extrapolated and a use of 5.6L pure alcohol per year per inhabitant aged 15+ has been estimated in Belgium. The comparison with available information on drinking habits of the Belgian population further demonstrated the usefulness of the wastewater-based epidemiology approach.

Conclusions: This is the largest wastewater-based epidemiology study monitoring alcohol consumption to date, demonstrating that objective and quick information on spatio-temporal trends in alcohol consumption on a local and (inter)national scale can be obtained.
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http://dx.doi.org/10.1016/j.drugalcdep.2016.01.002DOI Listing
March 2016

Critical review on the stability of illicit drugs in sewers and wastewater samples.

Water Res 2016 Jan 21;88:933-947. Epub 2015 Oct 21.

Eawag, Swiss Federal Institute of Aquatic Science and Technology, CH 8600 Dübendorf, Switzerland. Electronic address:

Wastewater-based epidemiology (WBE) applies advanced analytical methods to quantify drug residues in wastewater with the aim to estimate illicit drug use at the population level. Transformation processes during transport in sewers (chemical and biological reactors) and storage of wastewater samples before analysis are expected to change concentrations of different drugs to varying degrees. Ignoring transformation for drugs with low to medium stability will lead to an unknown degree of systematic under- or overestimation of drug use, which should be avoided. This review aims to summarize the current knowledge related to the stability of commonly investigated drugs and, furthermore, suggest a more effective approach to future experiments. From over 100 WBE studies, around 50 mentioned the importance of stability and 24 included tests in wastewater. Most focused on in-sample stability (i.e., sample preparation, preservation and storage) and some extrapolated to in-sewer stability (i.e., during transport in real sewers). While consistent results were reported for rather stable compounds (e.g., MDMA and methamphetamine), a varying range of stability under different or similar conditions was observed for other compounds (e.g., cocaine, amphetamine and morphine). Wastewater composition can vary considerably over time, and different conditions prevail in different sewer systems. In summary, this indicates that more systematic studies are needed to: i) cover the range of possible conditions in sewers and ii) compare results more objectively. To facilitate the latter, we propose a set of parameters that should be reported for in-sewer stability experiments. Finally, a best practice of sample collection, preservation, and preparation before analysis is suggested in order to minimize transformation during these steps.
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http://dx.doi.org/10.1016/j.watres.2015.10.040DOI Listing
January 2016

A data-independent acquisition workflow for qualitative screening of new psychoactive substances in biological samples.

Anal Bioanal Chem 2015 Nov 22;407(29):8773-85. Epub 2015 Sep 22.

Toxicological Center, Department of Pharmaceutical Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.

Identification of new psychoactive substances (NPS) is challenging. Developing targeted methods for their analysis can be difficult and costly due to their impermanence on the drug scene. Accurate-mass mass spectrometry (AMMS) using a quadrupole time-of-flight (QTOF) analyzer can be useful for wide-scope screening since it provides sensitive, full-spectrum MS data. Our article presents a qualitative screening workflow based on data-independent acquisition mode (all-ions MS/MS) on liquid chromatography (LC) coupled to QTOFMS for the detection and identification of NPS in biological matrices. The workflow combines and structures fundamentals of target and suspect screening data processing techniques in a structured algorithm. This allows the detection and tentative identification of NPS and their metabolites. We have applied the workflow to two actual case studies involving drug intoxications where we detected and confirmed the parent compounds ketamine, 25B-NBOMe, 25C-NBOMe, and several predicted phase I and II metabolites not previously reported in urine and serum samples. The screening workflow demonstrates the added value for the detection and identification of NPS in biological matrices.
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http://dx.doi.org/10.1007/s00216-015-9036-0DOI Listing
November 2015

Evaluation of an Assertive Continuing Care Program for Hispanic Adolescents.

Glob J Health Sci 2015 Feb 24;7(5):106-16. Epub 2015 Feb 24.

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Purpose: This study evaluated an Adolescent Community Reinforcement Approach (A-CRA) and Assertive Continuing Care (ACC) program targeting Hispanic adolescents at risk for substance abuse.

Method: The Clinic for Education, Treatment, and Prevention of Addiction (CETPA, Inc.), a behavioral health provider offering culturally appropriate substance use and mental health services, carried out the intervention. We examined longitudinal substance use data in relation to time spent in the program and possible confounders.

Results: We analyzed data from 72 adolescent clients collected between 2010 and 2012. Self-reported data were evaluated to determine if time spent in the program was associated with substance use reduction. The data were correlated, zero-inflated, and overdispersed; consequently, we employed a mixed-effects zero-inflated negative-binomial model. Time spent in CETPA's program was significantly associated with reductions in the number of days of substance use (p=.039), but not with the likelihood of fully abstaining from use (p=.290). For non-abstinent participants who spend a year in the program, our models revealed an average decline of 46% in reported days of substance use.

Conclusions: A culturally tailored and age-appropriate substance abuse program for Hispanic adolescents resulted in a significant reduction of the numbers of days using alcohol, drugs, or other illicit substances. The A-CRA/ACC approach can yield successful results in culturally diverse settings.
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http://dx.doi.org/10.5539/gjhs.v7n5p106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803868PMC
February 2015

Liquid chromatography-quadrupole time-of-flight mass spectrometry for screening in vitro drug metabolites in humans: investigation on seven phenethylamine-based designer drugs.

J Pharm Biomed Anal 2015 Oct 12;114:355-75. Epub 2015 Jun 12.

Toxicological Center, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.

Phenethylamine-based designer drugs are prevalent within the new psychoactive substance market. Characterisation of their metabolites is important in order to identify suitable biomarkers which can be used for better monitoring their consumption. Careful design of in vitro metabolism experiments using subcellular liver fractions will assist in obtaining reliable outcomes for such purposes. The objective of this study was to stepwise investigate the in vitro human metabolism of seven phenethylamine-based designer drugs using individual families of enzymes. This included para-methoxyamphetamine, para-methoxymethamphetamine, 4-methylthioamphetamine, N-methyl-benzodioxolylbutanamine, benzodioxolylbutanamine, 5-(2-aminopropyl) benzofuran and 6-(2-aminopropyl) benzofuran. Identification and structural elucidation of the metabolites was performed using liquid chromatography-quadrupole-time-of-flight mass spectrometry. The targeted drugs were mainly metabolised by cytochrome P450 enzymes via O-dealkylation as the major pathway, followed by N-dealkylation, oxidation of unsubstituted C atoms and deamination (to a small extent). These drugs were largely free from Phase II metabolism. Only a limited number of metabolites were found which was consistent with the existing literature for other phenethylamine-based drugs. Also, the metabolism of most of the targeted drugs progressed at slow rate. The reproducibility of the identified metabolites was assessed through examining formation patterns using different incubation times, substrate and enzyme concentrations. Completion of the work has led to a set of metabolites which are representative for specific detection of these drugs in intoxicated individuals and also for meaningful evaluation of their use in communities by wastewater-based drug epidemiology.
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http://dx.doi.org/10.1016/j.jpba.2015.06.016DOI Listing
October 2015

Sewage-based epidemiology in monitoring the use of new psychoactive substances: Validation and application of an analytical method using LC-MS/MS.

Drug Test Anal 2015 Sep 6;7(9):812-8. Epub 2015 Feb 6.

Toxicological Center, Department of Pharmaceutical Sciences, Campus Drie Eiken, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.

Sewage-based epidemiology (SBE) employs the analysis of sewage to detect and quantify drug use within a community. While SBE has been applied repeatedly for the estimation of classical illicit drugs, only few studies investigated new psychoactive substances (NPS). These compounds mimic effects of illicit drugs by introducing slight modifications to chemical structures of controlled illicit drugs. We describe the optimization, validation, and application of an analytical method using liquid chromatography coupled to positive electrospray tandem mass spectrometry (LC-ESI-MS/MS) for the determination of seven NPS in sewage: methoxetamine (MXE), butylone, ethylone, methylone, methiopropamine (MPA), 4-methoxymethamphetamine (PMMA), and 4-methoxyamphetamine (PMA). Sample preparation was performed using solid-phase extraction (SPE) with Oasis MCX cartridges. The LC separation was done with a HILIC (150 x 3 mm, 5 µm) column which ensured good resolution of the analytes with a total run time of 19 min. The lower limit of quantification (LLOQ) was between 0.5 and 5 ng/L for all compounds. The method was validated by evaluating the following parameters: sensitivity, selectivity, linearity, accuracy, precision, recoveries and matrix effects. The method was applied on sewage samples collected from sewage treatment plants in Belgium and Switzerland in which all investigated compounds were detected, except MPA and PMA. Furthermore, a consistent presence of MXE has been observed in most of the sewage samples at levels higher than LLOQ.
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http://dx.doi.org/10.1002/dta.1777DOI Listing
September 2015

Temporal analysis of the cocaine metabolite benzoylecgonine in wastewater to estimate community drug use.

J Forensic Sci 2012 Sep 17;57(5):1349-53. Epub 2012 Apr 17.

Institute for Forensic Science, Texas Tech University, Lubbock, TX 79409, USA.

Indirect estimation methods of cocaine consumption may not reflect the real extent of cocaine use. Another approach is sewage epidemiology. This direct approach is based on analysis of a stable cocaine metabolite, benzoylecgonine (BE), in wastewater. Influent to the Lubbock (Texas) Water Reclamation Plant was sampled twice a week to assess weekly variations in estimates of cocaine consumption over a 5-month period. BE was extracted from influent wastewater samples using solid phase extraction and analyzed using gas chromatography/mass spectrometry. Measured concentrations of BE were converted to cocaine equivalents; the estimated average daily consumption of cocaine during the study period was 1152 ± 147 g. Based on BE concentrations and sewage epidemiology, higher cocaine consumption was observed on weekends compared to weekdays (p < 0.0003). This method was effective in monitoring BE in wastewater and could be used to complement survey data in estimating cocaine use at a local level.
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http://dx.doi.org/10.1111/j.1556-4029.2012.02135.xDOI Listing
September 2012