Determination of ziprasidone by UPLC-MS-MS and its application to a pharmacokinetic study of chinese schizophrenics

摘要

A simple, rapid, and selective method to determine the concentration of ziprasidone hydrochloride in schizophrenics~' plasma using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) was developed and validated. The UPLC separation was carried out with an Acquity UPLC BEH C_(18) column (50 × 2.1 mm i.d., 1.7 μm particle size). The mobile phase consisted of methanol-water (50:50, v/v; the water included 15 mM NH_4Ac and 0.125% acetic acid). The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) at m/z 412.82 → 193.75 for ziprasidone and m/z 236.87 → 193.76 for the internal standard, carbamazepine. Solid-phase extraction was used to extract ziprasidone hydrochloride and carbamazepine from plasma. Ziprasidone and the internal standard eluted as sharp, symmetrical peaks with retention times of 1.24 ± 0.01 min and 1.74 ± 0.02 min, respectively. Calibration curves of ziprasidone at concentrations ranging from 0.7 to 400 ng mL~(-1) exhibited excellent linearity (r = 0.9995), with a lower limit of quantification of 0.7 ng mL~(-1). Intra- and inter-day relative standard deviations were less than 7.75% RSD and 5.43% RSD, respectively. The extraction recovery was above 81.3%. The described assay method showed acceptable precision, accuracy, linearity, stability, and specificity and can be used for pharmacokinetic studies.