SPE–UPLC–MS/MS method for sensitive and rapid determination of aripiprazole in human plasma to support a bioequivalence study

An improved and rugged UPLC–MS/MS method has been developed and validated for sensitive and rapid determination of aripiprazole in human plasma using aripiprazole-d8 as the internal standard (IS). The analyte and IS were extracted from 100 μL of human plasma by solid-phase extraction using Phenomenex Strata-X (30 mg, 1 cc) cartridges. Chromatography was achieved on an Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) analytical column using methanol: 10 mM ammonium formate (85:15, v/v) as the mobile phase with isocratic elution. Quantitation was done using multiple reaction monitoring in the positive ionization mode. The linearity of the method was established in the concentration range 0.05–80 ng/mL. The mean extraction recovery was greater than 96% across QC levels, while intra- and inter batch accuracy and precision (% CV) values ranged from 97.4 to 101.9% and from 1.20 to 3.72% respectively. The relative matrix effect in eight different lots of plasma samples, expressed as % CV for the calculated slopes of calibration curves was 1.08%. The stability of aripiprazole was studied under different storage conditions. The validated method was used to support a bioequivalence study of 10 mg aripiprazole formulation in 36 healthy Indian subjects.