Metabolism of ADB-4en-PINACA in Zebrafish and Rat Liver Microsomes Determined by Liquid Chromatography–High Resolution Mass Spectrometry

作者：Xinze Liu, Wei Liu, Ping Xiang, Taijun Hang, Yan Shi, Lin-Na Yue, Hui Yan · 发表于：Journal of Analytical Chemistry · 年份：2022 · DOI：10.1134/s1061934822080184 · 被引用次数：12 · 研究领域：Cannabis and Cannabinoid Research、Forensic Toxicology and Drug Analysis、Neurotransmitter Receptor Influence on Behavior

Abstract Metabolic models can be useful for rapid identification of suitable analytical targets to aid in the detection of new psychoactive substances (NPS) in human biological samples. In vitro and in vivo metabolic studies of the synthetic cannabinoid ADB-4en-PINACA were carried out using zebrafish and rat liver microsome models. Seventeen phase-I metabolites, including seventeen metabolites generated from rat liver microsomes and fourteen metabolites from zebrafish, were identified and structurally characterized by liquid chromatography–high resolution mass spectrometry. The main metabolic pathways of the phase-I metabolism included hydroxylation, N-dealkylation, amide hydrolysis, ketone formation from the t-butyl and aliphatic chains, oxidation of the N-double-bond, amide hydrolysis combined with dehydrogenation, and amide hydrolysis followed by hydroxylation, as well as dehydrogenation and N-dealkylation. Hydroxylation (M3), ketone (M10), and dihydrodiol (M15) metabolites can be recommended as metabolic markers for ADB-4en-PINACA. These findings identify the zebrafish model as a promising tool for elucidating the metabolism of NPS.