Comparative Analysis and Structure Identification of Oxidative Metabolites and Hydrogenation Metabolite Enantiomers for 2-Fluorodeschloroketamine

Abstract

In this study, we used solid-phase extraction (SPE) with liquid chromatography-ion trap/time-of-flight mass spectrometry (LC-IT/TOF-MS) to analyze 2-fluorodeschloroketamine (2-FDCK) metabolites in human urine. The complete set of oxidative metabolites was identified, with 17 compounds divided into four groups. Furthermore, we examined the hydroxy substitution site after oxidative metabolism with theoretical calculation and 2-FDCK NMR data. We clarified the correlation of the oxidative metabolic sites with the electron cloud density in the structure. Additionally, two enantiomers of dihydro-2-fluorodeschloroketamine (dihydro-2-FDCK) were determined by a lab-made dihydro-2-FDCK hydrochloride reference substance. Their configurations were determined via nuclear magnetic resonance (NMR) spectrometry data prediction of the ACD Labs-Structure Elucidator Suite software and theoretical calculation. Moreover, the stereoselectivity of the related enzymes in hydrogenation metabolism in vivo was clarified. These findings provide an important reference for analyzing other oxidative metabolites, laying the foundation for future analysis, prediction, elucidation, and identification of the latest ketamine-type NPS metabolites.