Metabolite Profiling and Pathway Elucidation of 2-Fluorodeschloroketamine and 2-Fluoro-N-ethylketamine in Rats Using HPLC-QTOF Mass Spectrometry
Yujie Zhang, Qing-Hong Wang, Yan-Jun Wang, Yongfu Wu, Xun Tian, Yong Dai, Yugang Cai
Metabolites June 1, 2026 DOI: 10.3390/metabo16060394 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Sprague-Dawley rats |
| Interventions | 2-FDCK 2-FXE |
| Dose | 0.045 mg/kg |
| Duration | Single dose; samples collected at 1 h and 2 h post-dosing |
| Key findings | Metabolic pathways of 2-FDCK and 2-FXE were mostly consistent, but significant differences occurred in metabolic reaction types, metabolite formation times, and response intensities, likely due to chemical structural differences. These findings offer clues for understanding drug effect disparities and provide a reference for forensic toxicological evaluation. |
Abstract
Highlights What are the main findings? A HPLC-QTOF/MS system was used to detect potential metabolites of 2-FDCK and 2-FXE in rats, determine metabolic pathways, and analyze metabolic differences. After single intraperitoneal injection administration of the drugs, samples were collected at 1 h and 2 h post-dosing. Metabolites were identified through database searches and secondary mass spectrometry fragment ion analysis, allowing inference of metabolic pathways. Comparative analysis showed that while metabolic pathways were largely consistent between the two groups, there were significant differences in metabolic reaction types, metabolite formation times, and metabolite response intensities, likely due to chemical structural differences. What are the implications of the main findings? The findings offer crucial clues for understanding drug effect disparities between the two compounds. They provide a reference for forensic toxicological evaluation of new psychoactive substances in the phencyclidine class. Abstract
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.