A rapid and selective LC–MS/MS method for the quantification of aripiprazole in beagle dog plasma and its application to a pharmacokinetic study

Abstract

A rapid, selective and cost-effective ultra-performance liquid chromatography-tandem mass spectrometric method was developed and validated for the determination of aripiprazole in beagle dog plasma. UPLC analysis was carried out under the following conditions: a Kinetex C18 column (50 mm × 2.1 mm i.d., 1.7 µm particle size), mobile phase of acetonitrile and 5 mM ammonium acetate with gradient elution and flow rate of 0.2 mL/min. Aripiprazole and an internal standard (papaverine) were extracted by liquid–liquid extraction with ethyl ether. The total run time was 4 min. The analyte was detected using an electrospray ionization tandem mass spectrometry in the multiple reaction monitoring mode. The chromatograms showed good resolution and sensitivity as well as no interference from the beagle dog plasma. The calibration curves were linear over the concentration range, 1.0–100 ng/mL using a 100 μL plasma sample, with correlation coefficients >0.998. The intra- and inter-day assay precision as well as the accuracy fulfilled the international requirements. The lower limit of quantification for aripiprazole in beagle dog plasma was 1 ng/mL, which is sensitive enough for pharmacokinetic studies. Stability studies revealed that aripiprazole in beagle dog plasma was stable during storage as well as during the assay procedure. The validated method was successfully applied to an examination of the pharmacokinetics of aripiprazole in beagle dogs following a single oral dose of an aripiprazole (10 mg) tablet. This method allows laboratory researchers to simply determine aripiprazole in plasma.