Development of a UPLC–MS/MS method for determination of pimavanserin tartrate in rat plasma: Application to a pharmacokinetic study

A simple, rapid and sensitive method based on an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) has been developed and validated for the determination of pimavanserin in rat plasma. The analyte was extracted by protein precipitation with methanol and separated on an ACQUITY BEH C(18) column (100 × 2.1 mm, 1.7 µm; Waters, USA), with an isocratic elution of acetonitrile-water containing 10 mM ammonium acetate (70:30, v/v), at a flow rate of 0.2 mL/min for 2.5 min. The analyte and clarithromycin (the internal standard) were detected and quantified in positive ion mode using multiple reaction monitoring transitions at m/z 428.2 → 223.0 for pimavanserin and m/z 748.5 → 589.5 for clarithromycin. Relative coefficient (r) for the calibration curve was more than 0.9980. The intra-day and inter-day precisions (relative standard deviation, RSD%) were less than 13.3% and 10.5%, respectively, and the accuracy (relative error, RE%) was within ± 11.5%. The analytical method was successfully applied to a routine pharmacokinetic study of pimavanserin in rats after oral administration at the dose of 10 mg/kg.