ADB-BUTINACA, a synthetic cannabinoid receptor agonist: overview of its presence in the "Chimique" in Mayotte (2025)

The emergence of new psychoactive substances (NPS) has made illicit drugs a major health issue. The largest family of NPS is that of synthetic cannabinoid receptor agonists (SCRAs). Due to their widespread use, security authorities are working to strengthen their protocols for detecting, managing, and preventing abuse. Wastewater-based epidemiology, which focuses on drug metabolites, complements seizures and questionnaires in this regard. In this context, we present data on ADB-BUTINACA, a SCRA detected during the "Chasse-marée" study conducted in Mayotte, a French overseas territory located in the Mozambique Channel. The aim of this article is to identify and select ADB-BUTINACA metabolites relevant as target residues of this SCRA to estimate population exposure from wastewater. Using LC-HRMS, this SCRA (along with other SCRAs) was detected in "Chimique" samples (the term used for illicit substances in circulation in Mayotte) on 24 occasions during seven of the eight sampling campaigns conducted as part of the study (2022-2023). We then conducted a study on its metabolism using in vitro human liver microsome incubation experiments and LC-HRMS analysis and discussed its most relevant biomarker. Among the 26 metabolites identified, two resulting from the mono-hydroxylation of the n-butyl tail of ADB-BUTINACA (C(18)H(26)N(4)O(3), HRMS target [M+H]+ m/z 347.2078) are considered the most promising biomarkers. This assessment is based on the relatively high intensity of the chromatographic peak observed in vitro (41.7% and 34.2%, respectively) and on the assumption that this type of product is persistent in wastewater. Their practical analytical relevance in subsequent studies still needs to be validated by assessing their toxicological significance and stability in wastewater. These two metabolites constitute an initial proposal for targets for monitoring ADB-BUTINACA in wastewater, subject to verification of their persistence, in order to improve knowledge of these compounds. [Author's abstract]