Structural identification and metabolic profiling of the new psychoactive substance 2-fluoro-2-oxo-PCPr using NMR and LC-QTOF-MS.
Forensic science international – November 10, 2025
Source: PubMed
Summary
A newly identified psychoactive substance, 2-fluoro-2-oxo-PCPr, was found to exist in two interconverting rotameric forms, a unique molecular characteristic confirmed by GIAO-DFT NMR calculations. Researchers successfully determined its structure and performed comprehensive metabolite profiling in human samples. Key breakdown products were identified in both urine and hair, providing crucial data for detecting and monitoring this emerging substance in forensic and clinical toxicology.
Abstract
Fluorinated analogs of ketamine, such as 2-fluoro-deschloroketamine and its isomers, have recently emerged as dissociative anesthetics that act through multiple central nervous system pathways. As their prevalence continues to increase, metabolic studies are critical to confirm their use in suspected cases of abuse. 2-Fluoro-N-propylnordeschloroketamine (2-fluoro-2-oxo-PCPr), in which a propyl group replaces the methyl group of 2-fluoro-deschloroketamine, was seized by investigative authorities in 2025. In this study, we determined the chemical structure of 2-fluoro-2-oxo-PCPr using nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Notably, the duplicated NMR signals in the N-propyl region indicated the presence of two interconverting rotameric forms in an approximately 2:1 equilibrium. The structures of the individual rotamers were confirmed by gauge-including atomic orbital (GIAO)-based density functional theory (DFT) NMR calculations. Metabolite profiling was conducted on suspected abusers' urine using LC-QTOF-MS in conjunction with MetabolitePilot™ software. The identified metabolic pathways included glucuronidation, desaturation, hydrogenation of the cyclohexanone ring, hydroxylation, carboxylation, and N-depropylation. Urine and hair collected from the abusers were analyzed using LC-MS/MS with multiple reaction monitoring transitions to enhance the detection limits. The primary metabolite, nor-2-fluoro-2-oxo-PCPr was detected in both urine and hair, supporting its potential utility as a long-term biomarker. This is the first study to identify the structure of 2-fluoro-2-oxo-PCPr and its metabolites in urine and hair. With the increasing new psychoactive substances abuse and diagnostic challenges, these findings provide key data for detecting and monitoring emerging psychoactive substance in forensic and clinical toxicology.