Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany.
2 papers in the library · 5 citations · publishing 2024-2025
Five deschloroketamine derivatives—deschloro-N-cyclopropyl-ketamine, deschloro-N-ethyl-ketamine, deschloro-N-isopropyl-ketamine, deschloro-N-propyl-ketamine, and deschloroketamine—are primarily metabolized through N-dealkylation, hydroxylation, multiple oxidations, and combinations, plus glucuronidation and N-acetylation. In total, 29 phase I and 10 phase II metabolites were detected in rat urine after a 2 mg/kg body weight dose, using liquid chromatography high-resolution tandem mass spectrometry and gas chromatography-mass spectrometry. For the LC-HRMS/MS standard urine screening approach, compound-specific metabolites were identified and confirmed in pooled human liver microsomes for all derivatives except deschloro-N-cyclopropyl-ketamine. The GC-MS approach detected only non-specific acetylated N-dealkylation metabolites.
Five deschloroketamine derivatives and most of their metabolites remain sufficiently stable in raw wastewater to serve as analytical targets for wastewater-based epidemiology. After incubating the parent compounds, rat urine, or rat feces in untreated influent wastewater for 24 hours, all parent compounds, seven Phase I metabolites, and one Phase II metabolite were detected in rat feces. Peak areas of Phase II N- and O-glucuronides decreased markedly, consistent with earlier findings that Phase II conjugates are unstable in wastewater and unsuitable as biomarkers. The results indicate that the parent drugs and their Phase I metabolites can be used for wastewater surveillance of these new psychoactive substances.