Quantitative Determination of Brexpiprazole in Rat Plasma by UPLC-MS/MS and Application to a Pharmacokinetic Study

An ultra-performance liquid chromatography tandem mass spectrometry method (UPLCMS/MS) was developed and validated to detect brexpiprazole in rat plasma with aripiprazole as internal standard (IS). A single step of protein precipitation was adopted for samples preparation with acetonitrile. The chromatographic separation was performed on an acquity UPLC BEH C18 column (2.1 x 50 mm, 1.7 mu m) with a gradient mobile phase consisting of acetonitrile and 0.1% formic acid, pumped at the rate of 0.4 mL/min. The retention time of brexpiprazole and IS were 1.99 and 2.57 min, respectively. The analytes were detected using a triple quadrupole mass spectrometer in multi-reaction-monitoring (MRM) mode for target fragment ions m/z 434.3 -> 273.4 for brexpiprazole and m/z 448.2 -> 285.2 for IS. The method was validated in the linear range of 5-1000 pg/mL with acceptable inter-and intra-day precision, accuracy and stability. The method was successfully applied to pharmacokinetic study after intragastric administration of brexpiprazole in rat.