Development and Validation of an LC–ESI-MS Method for Quantitative Determination of Aripiprazole in Human Plasma and an Application to Pharmacokinetic Study

A selective, sensitive, high pressure liquid chromatography–posi-tive electrospray ionization tandem mass spectrometry method was developed and validated for the quantification of aripiprazole in human K2EDTA plasma using zolpidem tartrate as an internal stand-ard. The analyte and internal standard were extracted from human plasma by solid-phase extraction using methanol. The eluted samples were chromatographed on a Grace Smart RP 18 4.6 3 100 mm, 3 m column by using a 95:5 v/v mixture of methanol and ammonium acetate buffer (30 mM, pH 5.0+ 0.05) as a gradient mobile phase at a flow rate of 0.6 mL/min, and analyzed by mass spectrometry in the multiple reaction monitoring mode using the [M 1 H]1 ions m/z 448.03! 285.14 for aripiprazole and m/z 308.13! 235.25 for the internal standard (zolpidem tartrate), re-spectively. Calibration plots were linear over the concentration range of 0.20 to 60.01 ng/mL. Intra-day and inter-day precision (percent coefficient of variation) and accuracy (percent nominal) for quality control samples (0.60, 30.60 and 45.59 ng/mL) ranged between 2.28 and 8.93 % and between 92.50 and 107.07%, respect-ively. Extraction recovery of aripiprazole from plasma was in the range 75.56–79.57%; mean recovery was 77.35%. The main phar-macokinetic parameters were Tmax 5 (4.00+ 2.336) Cmax 5 (55.16+ 13.490) and AUC5 (1846.28+ 484.686)