Determination of Enantiomers of Deschloroketamine and Its Metabolites in Wistar Rat Brains.

Deschloroketamine (DXE) is a dissociative new psychoactive substance whose enantiomers and metabolites may exhibit distinct pharmacological and toxicological profiles. Reliable analytical methods enabling the chiral determination of DXE and its metabolites in biological matrices are thus essential. In this study, we evaluated supercritical fluid chromatography coupled to tandem mass spectrometry (SFC‑MS/MS) and capillary zone electrophoresis with ultraviolet detection (CZE‑UV) for the enantioselective analysis of DXE and its major metabolites in rat brain tissue. SFC using polysaccharide‑based chiral stationary phases provided baseline separation of the hydroxylated and demethylated metabolites, but severe peak distortion of DXE enantiomers prevented their quantification. Therefore, quantitative analysis was performed by CZE employing carboxymethyl‑β‑cyclodextrin as a chiral selector and a high‑sensitivity Z‑shaped detection cell. Analysis of brain tissue samples obtained following high-dose administration revealed near equimolar concentrations of the DXE enantiomers and a higher concentration of (R)-norDXE relative to (S)-norDXE. In this particular case, the combined use of SFC‑MS/MS and CZE‑UV provided a practical workflow for the chiral profiling of DXE and its metabolites in complex biological matrices.