STUDIES ON IN-VIVO PROCESS OF THE ENANTIOMERS OF NICARDIPINE IN RABBIT BY COUPLED CHIRAL AND ACHIRAL HPLC

AIM　To study the differences of the pharmacokinetics and tissue distribution of two enantiomers of nicardipine in the rabbit. METHODS　Biological samples were diluted by 1 mol·L^-1 NaOH solution and extracted with n-hexane - ethyl acetate (1:1). The concentrations of S-nicardipine and R-nicardipine in samples were determined by coupled achiral C₁₈ column (150 mm×4.6 mm, 5 μm) and chiral OJ column (250 mm×4.6 mm, 10 μm) chromatography. RESULTS　The racemic nicardipine and the enantiomers in sample were separated well by the coupled system. The linear range was 55-550 ng·mL^-1 for both enantiomers. The within-day and between-days RSD (n=5) were 5.25% and 8.97%, and the relative recoveries were 99.99% and 97.10% for R- and S- enantiomer, respectively. The mean T_max, C_max and AUC values were (2.49±0.03) h, (134±2) ng·mL^-1 and (1082±32) ng·mL^-1·h for S-nicardipine and (1.24±0.05) h, (109±2) ng·mL^-1 and (778±22) ng·mL^-1·h for R-nicardipine. The concentration of S-nicardipine were generally higher than that of R-nicardipine in main target tissues and cells. CONCLUSION There were significant differences between the two enantiomers of nicardipine in rabbit in pharmacokinetics and tissue distribution.