Phase I Metabolism of Synthetic Cannabinoid Receptor Agonist PX-1 (5F-APP-PICA) via Incubation with Human Liver Microsomes and UHPLC-HRMS.

Phase I Metabolism of Synthetic Cannabinoid Receptor Agonist PX-1 (5F-APP-PICA) via Incubation with Human Liver Microsomes and UHPLC-HRMS. Biomed Chromatogr. 2019 Dec 21;:e4786 Authors: Presley BC, Logan BK, Jansen-Varnum SA Abstract Studies of the metabolic and pharmacological profiles of indole carboxamide synthetic cannabinoids (a prevalent class of New Psychoactive Substances) are critical in ensuring that their use can be detected through bioanalytical testing. The present study provides the determination of the in vitro Phase I metabolism of one such compound, PX-1 (5F-APP-PICA), and appropriate markers to demonstrate human consumption. PX-1 was incubated with human liver microsomes, followed by analysis of the extracts via high-resolution mass spectrometry. A total of 10 metabolites were identified, with simultaneous defluorination and monohydroxylation of the pentyl side chain as the primary biotransformation product (M1). Additional metabolites formed were hydroxylation products of the indole and benzyl moieties; distal amide hydrolysis; N-desfluoropentyl; and carboxypentyl metabolites. Three monohydroxylated metabolites specific to PX-1 were identified and are reported for the first time in this study. The primary metabolite, M1, was further oxidized to M5, a carboxypentyl metabolite. M8 is PX-1-specific, possessing an intact fluoropentyl side chain. These three metabolites are the most suitable for implementation into bioa...
Source: Biomedical Chromatography : BMC - Category: Biomedical Science Authors: Tags: Biomed Chromatogr Source Type: research