DETERMINATION OF NIMODIPINE AND ITS PHARMACOKINETICS IN HUMAN PLASMA BY CAPILLARY GAS CHROMATOGRAPHY USING ELECTRON-CAPTURE DETECTION

AIM: To develope a capillary GC-ECD method for the study of phamacokinetics and relative bioavailability of nimodipine tablet in human body. METHODS: Chromatography was performed on a 25 m×0.2 mm ID 0.2 μm film thickness OV-101 fused-silica capillary column coupled with a 63Ni electron-capture detector. The carrier gas was highly pure nitrogen. The flow rate of carrier gas in the capillary column was 1.8 ml.min-1. The split ratio was 1∶33. The flow rate of make-up gas was 17 ml.min-1. The temperatures of the column, injector and detector were 260℃, 270℃ and 300℃, respectively. The internal standard was nitrendipine. After making alkaline with 1 mol.L-1 NaOH solution, the plasma was extracted with n-hexane — ethyl acetate (1∶1). RESULTS: A good linearity was obtained from 2.0 ng.ml^-1 to 150.0 ng.ml^-1 of nimodipine in human plasma with a correlation coefficient of 0.99989. The detection limit of nimodipine in human plasma was 0.1 ng.ml^-1. The extraction recovery was more than 80%. The pharmacokinetics of nimodipine was determined by this GC-ECD method following a single oral dose of 100 mg of two kinds of domestic nimodipine tablets given to each of 10 volunteers in an open randomized two-way crossover design. The results showed that the plasma concentration-time courses of the two kinds of tablets conformed to one compartment model. There was no significant difference between the two formulations in the AUC_0→∞, C_max and T_max. CONCLUSION: The established GC-ECD method was found to be a good method for determination of nimodipine in human plasma. The results of statistical analysis showed that the two formulations of nimodipine were biologically equivalent. The relative bioavailability of tablet A was 102.0% compared with that of tablet B.