A novel and robust analytical method for the quantification of perospirone in human plasma using an LC–MS/MS system with self-internal standard calibration

This study aims to establish a novel method for measuring perospirone in human plasma for therapeutic drug monitoring (TDM) by liquid chromatography-mass spectrometry (LC-MS) coupled with an automatic liquid chromatograph mass spectrometer coupler 9500 (LC-MS/MS-Mate 9500), which has been equipped with self-internal standard (SIS) calibration technology.A novel and attractive analytical calibration method designed for perospirone, calibration with SIS, was reported. After protein precipitation with acetonitrile-cyclopentanol (9:1, v/v) containing 1% NH3·H2O, LC-MS quantification of perospirone was performed by multiple reaction monitoring in the positive mode with quantitative and qualitative analysis of the ion pairs m/z 427.30 → 177.15 and 427.30 → 166.15 for perospirone and SIS. Chromatographic separation was accomplished in < 2.0 min on an Hypersil GOLDTM C18 column (2.1 mm × 50 mm, 3.0 μm) using a mobile methanol phase and 0.1% formic acid in water.This method showed good selectivity because no interfering peaks were observed in the plasma samples during the 2.0-min run time. The calibration curve range was 0.05-20 ng/mL, with a correlation coefficient of ≥ 0.9995. Intraday and interday accuracies were 98.3%-107.9%, respectively, with precision relative standard deviation values of < 10%. The matrix effects ranged from 92.7% to 96.1%, and extraction recoveries were between 97.3% and 108.8%. Finally, this method was successfully applied to routine clinical TDM for 142 patients. The perospirone plasma concentrations of the patients ranged between 0.07 and 10.96 ng/mL.This bioanalytical method can be used for the quantification of perospirone in human plasma by LC-MS/MS-Mate 9500 using perospirone itself as the SIS.