Determination of aripiprazole in rat plasma and brain using ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry

Aripiprazole is an important antipsychotic drug. A simple, sensitive and rapid ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and validated for the simultaneous quantification of this compound in rat plasma and brain homogenate. The analyte was extracted from rat plasma and brain homogenate using a weak cation exchange mixed-mode resin-based solid phase extraction. The compound was separated on an Agilent Eclipse Plus C₁₈ (2.1×50mm, 1.8μm) column using a mobile phase of (A) 0.1% formic acid aqueous and (B) acetonitrile with gradient elution. The analyte was detected in positive ion mode using multiple reaction monitoring. The method was validated and the specificity, linearity, limit of quantitation (LOQ), precision, accuracy, recoveries and stability were determined. The LOQ was 0.5ng/mL for aripiprazole in plasma and 1.5ng/g in brain tissue. The MS response was linear over the concentration range 0.5-100ng/mL for aripiprazole in plasma and 1.5-300ng/g in brain tissue. The precision and accuracy for intra-day and inter-day were better than 14%. The relative and absolute recoveries were above 72% and the matrix effects were low. This validated method was successfully used to quantify the rat plasma and brain tissue concentrations of the analyte following chronic treatment with aripiprazole.