biostudies-literatureUnknown11Cai YGThis study investigated the metabolic profiles of two isomeric psychoactive agents, methyl-ketamine [2-(ortho-tolyl)-2-(methylamino)cyclohexanone] and 2-oxo-PCE [2-(phenyl)-2-(ethylamino)cyclohexanone], in rats. Following oral administration, blood, liver, and urine samples were collected at timed intervals and analyzed via ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Metabolomic comparisons revealed distinct metabolic pathways driven by structural differences. Methyl-ketamine primarily underwent cyclohexanone hydroxylation, dehydration, N-demethylation, cyclohexanone carbonyl hydrogenation, and glucuronidation, with N-dealkylation as the dominant process. In contrast, 2-oxo-PCE metabolism involved carbonyl hydrogenation of cyclohForensic science international. Synergy100623https://www.ebi.ac.uk/biostudies/studies/S-EPMC12281064biostudies-literatureMetabolic patterns of new psychoactive substances: Methyl-ketamine and 2-oxo-PCE in rats using UHPLC-QTOF analysis.PMC12281064Wu YFWang QHCai YGFeng JYDai YWang YJMo YfalseMetabolic patterns of new psychoactive substances: Methyl-ketamine and 2-oxo-PCE in rats using UHPLC-QTOF analysis.This study investigated the metabolic profiles of two isomeric psychoactive agents, methyl-ketamine [2-(ortho-tolyl)-2-(methylamino)cyclohexanone] and 2-oxo-PCE [2-(phenyl)-2-(ethylamino)cyclohexanone], in rats. Following oral administration, blood, liver, and urine samples were collected at timed intervals and analyzed via ultrahigh performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Metabolomic comparisons revealed distinct metabolic pathways driven by structural differences. Methyl-ketamine primarily underwent cyclohexanone hydroxylation, dehydration, N-demethylation, cyclohexanone carbonyl hydrogenation, and glucuronidation, with N-dealkylation as the dominant process. In contrast, 2-oxo-PCE metabolism involved carbonyl hydrogenation of cycloh2025-01-01T00:00:00Z2025 Dec2026-03-27T16:22:36.725Z2025-08-31T03:05:15.794ZS-EPMC122810644069775910.1016/j.fsisyn.2025.100623