title: Monitoring MDMA metabolites in urban wastewater as novel biomarkers of consumption.
abstract: Consumption of 3,4-methylendioxymethamphetamine (MDMA) has been always estimated by measuring the parent substance through chemical analysis of wastewater. However, this may result in an overestimation of the use if the substance is directly disposed in sinks or toilets. Using specific urinary metabolites may overcome this limitation. This study investigated for the first time the suitability of a panel of MDMA metabolites as biomarkers of consumption, considering the specific criteria recently proposed, i.e. being detectable and stable in wastewater, being excreted in a known percentage in urine, and having human excretion as the sole source. A new analytical method was developed and validated for the extraction and analysis of MDMA and three of its main metabolites in wastewater. 24-h composite raw wastewater samples from three European cities were analysed and MDMA use was back-calculated. Results from single MDMA loads, 4-hydroxy-3-methoxymethamphetamine (HMMA) loads and from the sum of MDMA, HMMA and 4-hydroxy-3-methoxyamphetamine (HMA) loads were in line with the well-known recreational use of this drug: consumption was higher during the weekend in all cities. HMMA and HMA turned out to be suitable biomarkers of consumption; however, concentrations measured in wastewater did not resemble the expected pharmacokinetic profiles, quite likely due to the very limited information available on excretion profiles. Different options were tested to back-calculate MDMA use, including the sum of MDMA and its metabolites, to balance the biases associated with each single substance. Nevertheless, additional pharmacokinetic studies are urgently needed in order to get more accurate excretion rates and, therefore, improve the estimates of MDMA use.
authors.affiliation: Department of Environmental Health Sciences, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156, Milan, Italy; Department of Analytical Chemistry, Nutrition and Food Sciences, IIAA - Institute for Food Analysis and Research, University of Santiago de Compostela, Constantino Candeira S/N, 15782, Santiago de Compostela, Spain. Electronic address: iria.gonzalez@usc.es.
authors.forename: Iria
authors.initials: I
authors.lastname: González-Mariño
authors.affiliation: Department of Environmental Health Sciences, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156, Milan, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Zuccato
authors.affiliation: CIMAR/CIIMAR- Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Avenida General Norton de Matos, S/N, 4450-208, Matosinhos, Portugal; FCUP - Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007, Porto, Portugal.
authors.forename: Miquel M
authors.initials: MM
authors.lastname: Santos
authors.affiliation: Department of Environmental Health Sciences, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Via La Masa 19, 20156, Milan, Italy. Electronic address: sara.castiglioni@marionegri.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Castiglioni
mesh_terms: D015415:Biomarkers; D006801:Humans; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D062065:Wastewater
chemical_list: D015415:Biomarkers; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D062065:Wastewater
keywords: Biomarkers of consumption; Ecstasy; Liquid chromatography-mass spectrometry; Sewage analysis; Wastewater-based epidemiology