RAPID, SENSITIVE METHOD FOR THE DETERMINATION OF CINNARIZINE IN PLASMA BY LC-MS/MS AND IT’S APPLICATION TO PHARMACOKINETIC STUDY

摘要

Bioavailability of orally administered cinnarizine is typically low and variable due to high incidence of degradation. Many methods are available in public domain for the determination of Cinnarizine in plasma by RP-LC method but none published a LC-MS/MS method. Our objective is to develop a simple, rapid, sensitive bioanalytical method for the determination of Cinnarizine in human plasma by LC-MS/MS. Method has been developed for the Calibration curve range 0.4 to 100 ng/mL in plasma using LC-ESI-MRM detection on API 4000 coupled with SIL-HTC. Chromatography separation was achieved on Hypurity C18 column using Methanol: 5 mM Ammonium Acetate (pH 4.5) buffer in the ratio 95:5. Sample extraction was performed with methyl tertiary butyl ether and the detection was performed for MRM 369.250/ 167.150 along with labeled internal standard Cinnarizine D8. Method validation was performed for selectivity, matrix effect, recovery, precision, accuracy, ruggedness, haemolysis and lipemic effect and stabilities in aqueous as well as in plasma, all validation parameters found well within acceptance limits. Then the method is successfully applied to analyze subject samples a bioequivalence study to compare test with innovator formulation. Incurred sample reanalysis revealed that the method is reproducible and accurate.