Determination of R / S -enantiomers of methamphetamine and amphetamine in human hair with chiral stationary phase LC-MS/MS

Background As the synthetic abused drug with high addictive potential, methamphetamine (METH) and its major metabolite amphetamine (AMP) are chiral compounds. The S-enantiomer of METH is primarily abused because of its potent psychoactive effects, whereas the R-enantiomer may originate from the metabolism of selegiline, a prescription medication for Parkinson’s disease.Research design and methods This research aimed to develop a robust and reliable analytical method to distinguish illicit METH abuse from legal selegiline therapy. A novel, simplified chiral stationary phase liquid chromatography-tandem mass spectrometry (CSP-LC-MS/MS) method was developed and validated for the rapid determination of R- and S-enantiomers of METH and AMP in human hair, eliminating the need for derivatization pretreatment.Results Employing an Agilent Chiral-V column under isocratic conditions, the developed CSP-LC-MS/MS method achieved efficient baseline separation (resolution ≥2) and rapid quantification of the R/S enantiomers of METH and AMP within 10 min. Analysis of hair samples from three METH abusers revealed a predominance of the S-enantiomers. Conversely, only the R-enantiomer was detected in the hair of a selegiline user.Conclusions This research enables precise enantiomer differentiation, offering critical insights into drug metabolism and forensic discrimination between illicit METH abuse and legitimate selegiline treatment.