A liquid chromatography-electrospray ionization-tandem mass spectrometry method for quantitation of aripiprazole in human plasma

Abstract

A rugged liquid chromatographic-electrospray ionization-tandem mass spectrometric (LC-ESI-MS-MS) method was developed and validated for accurate monitoring of steady-state plasma aripiprazole. Haloperidol-d4 was chosen as the internal standard. ESI of aripiprazole and haloperidol-d4 yielded abundant MH+ ions, m/z 448 and 379, respectively. These ions were collisiondissociated to respective product ions of m/z 285 and 168. Ionsuppression experiments with blank plasma extracts showed substantial depressions of the product ions at retention times between 0.5 to 2 min, prohibiting development of a highthroughput LC-MS-MS method. A steep-gradient elution LC permitted a robust LC-ESI-MS-MS method with a 12-min analysis time. Aripiprazole was quantified from 0.2-mL aliquots of human plasma with acceptable precision and accuracy down to a lower limit of quantitation of 2 ng/mL. Aripiprazole was stable in plasma samples stored at room temperature for 24 h or exposed to three freeze-thaw cycles and in processed extracts stored at -20° C for six days or on the autosampler at 10° C for four days. The method has been successfully used for determinations of steady-state concentrations of aripiprazole in human subjects given daily oral doses of 15 mg. All measured concentrations were well within the quantitative range of 2 to 400 ng/mL.