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

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.