LC-MS/MS method for determination of omeprazole and its pharmacoldnetic characteristics in rabbits

AIM To establish a sensitive and selective LC-MS/MS method for the determination of omeprazole, and to study its pharmacokinetic characteristics in rabbits.METHODS The 0.5 mL of plasma samples were collected at 10,20,30,45,60,75,90,120,150,180,240,300 and 360 min after five Japanese rabbits were received a single intravenous administration of 2 mg·kg~(-1) omeprazole.Omeprazole was extracted from rabbit plasma by liquid-liquid extraction, and then analyzed on a Zorbax SB-C_(18)(150 mm×2.1 mm,5μm) column.The mobile phase consisted of acetonitrile -0.1%formic acid(40?60,V/V)at a flow rate of 0.3 mL·min~(-1).A Bruker Esquire HCT mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode.Quantification was performed using multiple reaction monitoring of the transitions m/z 346→198 and m/z 287→269 for omeprazole and the internal standard,respectively.RESULTS The linear calibration curves were obtained in the concentration range of 2-1 800μg·L~(-1).The lower limit of quantification was 2μg·L~(-1).The intra-day and inter-day relative standard deviations were less than 10%.The pharmacokinetics of omeprazole was as follows:AUC_(0→t)(922.925±214.175)μg·h·L~(-1),AUC_(0→∞)(936.61±205.95l)μg·h·L~(-1),t_(1/2)(1.88±0.802) h,V(6.501±4.067) L·kg~(-1),andρ_(max)(1 376.94±365.795)μg·L~(-1).CONCLUSION The pharmacokinetic parameters of omeprazole in rabbits are fitted to two compartment model,and omeprazoloe is eliminated fastly.The method is rapid,selective and is proved to be suitable for pharmacokinetic study for omeprazole.