Comparative Analysis and Structure Identification of Oxidative Metabolites and Hydrogenation Metabolite Enantiomers for 2-Fluorodeschloroketamine.
Xuan Luo, Di Zhang, Fang Zhang, Qiulian Luo, Kejian Huang, Xiaofeng Liu, Ning Yang, Junbo Li, Wentao Qiao, Lan Yang
Journal of analytical toxicology May 19, 2023 DOI: 10.1093/jat/bkad021 via PubMed
Summary
AI-generated from the abstractUsing mass spectrometry and theoretical calculations, 17 oxidative metabolites of the drug 2-fluorodeschloroketamine (2-FDCK) were identified in human urine and grouped into four categories. The study clarified how the site of oxidative metabolism relates to the electron cloud density in the molecule. Two mirror-image forms of a related compound, dihydro-2-FDCK, were distinguished using a lab-made reference standard and computational predictions. The work also revealed which enzymes favor particular molecular shapes during hydrogenation in the body. These findings provide a foundation for identifying metabolites of similar ketamine-type drugs.
Study at a glance
| Characteristics | Laboratory study Peer reviewed |
|---|---|
| Population | Human urine samples |
| Citations | 2 |
| Key finding | A complete set of 17 oxidative metabolites of 2-fluorodeschloroketamine was identified in human urine, and the stereoselectivity of enzymes in hydrogenation metabolism was clarified. |
Abstract
In this study, we used solid-phase extraction 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 nuclear magnetic resonance (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 using a laboratory-made dihydro-2-FDCK hydrochloride reference substance. Their configurations were determined via 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 new psychoactive substance metabolites.