Metabolite Profiling and Pathway Elucidation of 2-Fluorodeschloroketamine and 2-Fluoro-N-ethylketamine in Rats Using HPLC-QTOF Mass Spectrometry

Objectives: This study aimed to employ a High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry(HPLC-QTOF/MS) system to detect potential metabolites of 2-Fluorodeschloroketamine (2-FDCK) and 2-fluoro-N-ethylketamine (2-FXE) in rats, elucidate their metabolic pathways, and analyze the metabolic differences between the two compounds. Such exploration is vital for understanding their distinct drug effects and providing a reference for forensic toxicological assessment of new phencyclidine-class psychoactive substances. Methods: Twelve SD rats were randomly split into two groups. After a 12 h fast, each group was administered a single intraperitoneal injection of one drug at 0.045 mg/kg. At 1 h and 2 h post-dosing, the rats were euthanized, and blood, liver tissue, and urine samples were promptly collected. These samples underwent rapid solvent extraction for pretreatment and were then analyzed using HPLC-QTOF. Metabolites were identified through database searches and secondary mass spectrometry fragment ion analysis. Results: Comparative analysis of metabolite types, formation times, and chromatographic peak response intensities between the two groups showed that metabolic pathways were mostly consistent. However, significant differences were observed in metabolic reaction types, metabolite formation times, and response intensities, likely stemming from chemical structural disparities. Conclusions: The findings offer crucial insights into the drug effect differences between the two compounds and establish a valuable reference for forensic toxicological evaluation of new phencyclidine-class psychoactive substances.