Methoxphenidine (MXP), a dissociative anaesthetic derivative, is increasingly abused, but forensic and clinical data on its metabolism and enantiomers are limited. Researchers developed and validated achiral LC-MS/MS and chiral SFC-MS methods to quantify MXP and its primary metabolite, O-desmethyl-methoxphenidine (dmMXP), in rat serum and brain after a single subcutaneous dose of racemic MXP. Serum MXP peaked at 1600 ng/mL at 0.5 hours and decreased to 5.87 ng/mL at 24 hours; brain MXP peaked at 13200 ng/g at 0.5 hours and fell to 36.1 ng/g at 24 hours. (S)-MXP concentrations in brain appeared higher than (R)-enantiomer concentrations. The methods enable pharmacokinetic studies and provide tools for forensic and clinical toxicology.
The metabolism of the recreational drug 25E-NBOH was investigated in human liver microsomes, rat urine, and Cunninghamella elegans fungus. Using untargeted LC-HRMS/MS, 56 metabolites were annotated, many as isomers. Primary metabolic pathways included hydroxylation, O-demethylation, and N-debenzylation, followed by conjugation. Ten reference substances were synthesized; seven matched detected metabolites by retention time and MS/MS spectra, enabling structural assignment. The known psychoactive substance 2C-E was confirmed as a metabolite. Three main biomarkers are proposed. This work provides the first comprehensive metabolic profile of 25E-NBOH, supporting future pharmacological and toxicological studies and aiding clinical diagnosis of intoxication.