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Studies on the Stability and Microbial Biotransformation of Five Deschloroketamine Derivatives as Prerequisite for Wastewater-Based Epidemiology Screening. | LitMetric

Studies on the Stability and Microbial Biotransformation of Five Deschloroketamine Derivatives as Prerequisite for Wastewater-Based Epidemiology Screening.

Drug Test Anal

Department of Experimental and Clinical Toxicology and Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany.

Published: December 2024

AI Article Synopsis

Article Abstract

Wastewater (WW)-based epidemiology (WBE) is a powerful tool for screening and surveillance of drugs (of abuse) or new psychoactive substances (NPSs) in larger population. Since the drug market changes frequently, it is crucial for WBE to define screening and surveillance biomarkers considering drug metabolism and (microbial) stability. The aims of the presented work were first to identify metabolites, potentially serving as a WBE biomarker of five deschloroketamine derivatives (DCKDs) in rat feces samples after oral administration in addition to already known urinary metabolites, and second to elucidate the microbial biotransformation and WW stability of five DCKDs and their metabolites detected in urine and feces. Microbial biotransformation and stability of DCKD and their metabolites in WW were assessed by incubating parent compounds at 0.1 mg/L or rat urine or rat feces samples in freshly collected, untreated, influent WW over a period of 24 h. All samples were analyzed using liquid chromatography-high-resolution tandem mass spectrometry. All parent compounds, seven Phase I, and one Phase II metabolite were detected in rat feces samples. After WW incubations, all tested DCKD and their metabolites were still detectable at least in trace amounts, but particularly, peak areas of the Phase II N- and O-glucuronides showed a markable decrease. This is in line with previous findings where Phase II conjugates were identified to be unstable in WW and thus not recommended as a WW biomarker. Hence, incubations demonstrated that the five DCKD and most of their metabolites were sufficiently stable in WW influent and can thus be used as analytical targets in the context of WBE.

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http://dx.doi.org/10.1002/dta.3839DOI Listing

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