Source identification of amphetamine-like stimulants in Spanish wastewater through enantiomeric profiling

Andrea Estévez-Danta,Rosa Montes,Lubertus Bijlsma,Rafael Cela,Alberto Celma,Iria González-Mariño,Manuel Miró,Vanessa Gutmann,Unai Pérez De San Román-Landa,Ailette Prieto,Mireia Ventura,Rosario Rodil,José Benito Quintana

doi:10.1016/j.watres.2021.117719

Abstract

Amphetamine (AMP), methamphetamine (MAMP) and 3,4-methylenedioxymethamphetamine (MDMA) occur in wastewater not only as a result of illicit consumption, but also, in some cases, from prescription drug use or by direct drug disposal into the sewage system. Enantiomeric profiling of these chiral drugs could give more insight into the origin of their occurrence. In this manuscript, a new analytical methodology for the enantiomeric analysis of amphetamine-like substances in wastewater has been developed. The method consists of a solid-phase extraction (SPE) followed by liquid chromatography-triple quadrupole-tandem mass spectrometry (LC-MS/MS), which showed low quantification limits in the 2.4–5.5 ng L−1 range. The LC-MS/MS method was first applied to characterize a total of 38 solid street drug samples anonymously provided by consumers. The results of these analysis showed that AMP and MDMA trafficked into Spain are synthesized as racemate, while MAMP is exclusively produced as the S(+)-enantiomer. Then, the analytical method was employed to analyse urban wastewater samples collected from the wastewater treatment plants (WWTPs) of five different cities in 2018 and 2019. Consumption estimated through normalized population loads in wastewater showed an increased pattern of AMP use in the Basque Country. Furthermore, the enantiomeric profiling of wastewater samples was contrasted to lisdexamfetamine (LIS) and selegiline (SEL) prescription figures, two pharmaceuticals which metabolize to S(+)-AMP, and to R(-)-AMP and R(-)-MAMP, respectively. From this analysis, and considering uncertainties derived from metabolism and adherence to treatment, it was concluded that LIS is a relevant source of AMP in those cases with low wastewater loads, i.e. up to a maximum of 60% of AMP detected in wastewater in some samples could originate from LIS prescription, while SEL does not represent a significant source of AMP nor MAMP. Finally, removal efficiencies could be evaluated for the WWTP (serving ca. 860,000 inhabitants) with higher AMP influent concentrations. The removal of AMP was satisfactory with rates higher than 99%, whereas MDMA showed an average removal of approximately 60%, accompanied by an enrichment of R(-)-MDMA.

Highlights

Amphetamine (AMP), methamphetamine (MAMP) and 3,4-methylendioxymethamphetamine (MDMA) are synthetic derivatives of phenylethylamine that were used in the past to treat narcolepsy and spastic states of the gastrointestinal tract (Myerson, 1939)
An analytical methodology based on solid-phase extraction (SPE) and LC-MS/MS has been successfully developed for the determination of three chiral amphetamine-like substances in urban wastewater and street drug samples
The analyses of consumer-donated street drugs clearly indi cated that AMP and MDMA are produced as racemic mixtures for the Spanish illicit market, while MAMP is produced as the pure active S (+)-enantiomer

Summary

Introduction

Amphetamine (AMP), methamphetamine (MAMP) and 3,4-methylendioxymethamphetamine (MDMA) are synthetic derivatives of phenylethylamine that were used in the past to treat narcolepsy and spastic states of the gastrointestinal tract (Myerson, 1939). Hospital-related admissions and other epidemiological indicators, efforts to detect illicit drugs’ use in a fast and non-invasive way led to the first study using wastewater-based epidemiology (WBE) in 2005 by Zuccato et al (Zuccato et al, 2005). They estimated cocaine consumption in a specific population through the analysis of wastewater, as an complementary tool to the established epidemiological approaches. Addi tionally, WBE has been extended to estimate (unwanted) exposure to chemicals (Senta et al, 2020), such as pesticides (Rousis et al, 2016), flame retardants (Been et al, 2018; Castro et al, 2020), bisphenol A (Lopardo et al, 2019) and plasticizers (Estevez-Danta et al, 2021; Gonzalez-Marino et al, 2021, 2017), and more recently as a useful tool to follow and predict the evolution of COVID-19 (Ahmed et al, 2020; Alygizakis et al, 2020; Medema et al, 2020)

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