HIGH-THROUGHPUT DETERMINATION OF IVABRADINE FROM HUMAN PLASMA BY LC/MS/MS AND ITS APPLICATION TO PHARMACOKINETIC STUDIES

摘要

A rapid, selective, sensitive and reproducible liquid chromatographic method with mass spectrometric detection (LC-MS/MS) has been developed and validated for the analysis of a bradycardic agent, ivabradine, in human plasma.The samples (0.2 ml) were precipitated using perchloric acid 7% (0.1 ml) and the centrifuged supernatants were injected into HPLC system.Separation and detection of ivabradine were achieved using a C18 column and an MS/MS detector, with a positive electrospray ionization source. The ion transition monitored was 469---q177+262). Ivabradine gave a linear response ranging from 0.49 ng/ml to 49.30 ng/ml. The lower limit of quantification was established at 0.49 ng/ml. The analyte demonstrated good short-term, postpreparative and freeze-thaw stability. The validated method was subsequently applied to a pharmacokinetic study of ivabradine tablets on healthy volunteers.