Development and validation of UPLC-MS/MS method for determination of domperidone in human plasma and its pharmacokinetic application.

A sensitive, rapid and selective ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination and pharmacokinetic study of domperidone in human plasma. Diphenhydramine was used as the internal standard. Plasma sample pretreatment involved a one-step liquid-liquid extraction with a mixture of diethyl ether-dichloromethane (3:2, v/v). The analysis was carried out on an Acquity UPLC(TM) BEH C(18) column. The mobile phase consisted of methanol-water containing 10 mmol/L ammonium acetate and 0.5% (v/v) formic acid (60:40, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode via electrospray ionizationsource with positive mode. Each plasma sample was chromatographed within 2.1 min. The standard curves for domperidone were linear (r(2) ≥ 0.99) over the concentration range of 0.030-31.5 ng/mL with a lower limit of quantification of 0.030 ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 13% and accuracy (relative error) was from -7.6 to 1.2% at three quality control levels. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of domperidone in healthy Chinese volunteers after oral administration.