Metabolic patterns of new psychoactive substances: Methyl-ketamine and 2-oxo-PCE in rats using UHPLC-QTOF analysis.
Forensic science international. Synergy December 1, 2025 Yu-Gang Cai, Yan-Jun Wang, Yong-Fu Wu et al.
Two structurally similar psychoactive compounds, methyl-ketamine and 2-oxo-PCE, follow different metabolic routes in rats because of a single methyl group. After oral dosing, blood, liver, and urine were analyzed by high-resolution mass spectrometry. Methyl-ketamine mainly underwent N-demethylation and hydroxylation, while 2-oxo-PCE underwent carbonyl hydrogenation and deamination. The methyl group on methyl-ketamine’s aromatic ring blocked a hydrogenation step that occurred in 2-oxo-PCE, instead favoring hydroxylation and dehydration. Human urine samples showed comparable metabolite patterns, confirming the relevance of the rat model. Steric hindrance from small structural differences is a key determinant of how these substances are processed, which helps predict the behavior of related new psychoactive substances.