First enantioseparation and stereoselective metabolism of carisoprodol in rat liver microsomes

Carisoprodol, a widely prescribed muscle relaxant, is primarily metabolized into its main active metabolites, meprobamate and hydroxy carisoprodol. Despite its frequent use, the pharmacokinetics of carisoprodol have not been extensively studied, with the majority of research focusing on meprobamate. Moreover, even though carisoprodol has a stereogenic center, no chiral separation of carisoprodol has ever been reported in the literature. The present study describes the first enantioseparation of carisoprodol by a heart-cut bidimensional achiral-chiral chromatographic method in reversed-phase mode with a high-resolution mass spectrometry detector. The method was applied to the calculation of the depletion kinetics of the two enantiomers after incubation in rat liver microsomes. The results revealed that hepatic microsomes metabolize one enantiomer at a significantly faster rate than the other. The work provides valuable insights into the underexplored metabolism of carisoprodol, laying the ground for future pharmacological studies on the single enantiomers.