A Validated LC-MS/MS Method for the Determination of Perospirone in Human Plasma and Its Pharmacokinetic Application...

Perospirone hydrochloride hydrate is an atypical antipsychotic widely used in the management of schizophrenia. Reliable quantification of its plasma concentrations remains essential for pharmacokinetic characterization and dose optimization. A rapid, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated for the quantification of perospirone in human EDTA-K₂ plasma using perospirone-d ₈ as the internal standard (IS). Chromatographic separation was achieved on a Kinetex C18 analytical column (100 Å, 50 mm × 2.1 mm, 5 μm, 100 Å). The mobile phase consisted of an aqueous solution of 0.1% formic acid and 1 mM ammonium formate (MPA) and a solution of 95% acetonitrile containing 0.1% formic acid and 1 mM ammonium formate (MPB), delivered at a flow rate of 0.300 mL/min. The injection volume was 10 μL. Mass spectrometric detection was performed using electrospray ionization in positive-ion mode with multiple reaction monitoring (MRM). The method exhibited linearity over a concentration range of 0.0200-12.0 ng/mL. The validated method was successfully applied to fasting and postprandial pharmacokinetic studies following oral administration of perospirone hydrochloride tablets. The method demonstrates strong performance characteristics and practical utility, supporting its application in pharmacokinetic investigations, bioequivalence assessment, and clinical drug monitoring.