Liquid chromatography-tandem mass/mass spectrometry method for the quantification of rabeprazole in human plasma and application to a pharmacokinetic study.

摘要

A rapid, simple and sensitive reversed-phase high-performance liquid chromatographic-tandem mass/mass spectrometry (HPLC/MS/MS) method has been developed for the measurement of rabeprazole (CAS 117976-89-3) concentrations in human plasma and its use in bioavailability studies has been evaluated. The method was linear in the concentration range of 0.05-2.5 microg/ml. The lower limit of quantification (LLOQ) was 0.05 microg/ml in 1 ml plasma sample. The intra- and inter-day relative standard deviation across three validation runs over the entire concentration range was less than 8.2% and 7.53%, respectively. This method was successfully applied for the evaluation of pharmacokinetic profiles of rabeprazole tablet in 18 healthy volunteers. The main pharmacokinetic parameters obtained were: AUC(0-t) 1415.88 +/- 505.46 and 1457.44 +/- 524.40 ng x h/ml, AUC(0-infinity) 1439.10 +/- 507.47 and 1479.81 +/- 527.83 ng h/ml, C(max) 678.24 +/- 278.93 and 657.83 +/- 250.86 ng/ml, t1/2 1.48 +/- 0.19 and 1.38 +/- 0.24 h, t(max) 3.8 +/- 0.8 and 3.7 +/- 0.5 h for the test and reference formulations, respectively. No statistical differences were observed for C(max) and the area under the plasma concentration time curve for rabeprazole. 90% confidence limits calculated for C(max) and AUC from zero to infinity (AUC(0-infinity)) of rabeprazole were included in the bioequivalence range (0.8-1.25 for AUC).