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

ABSTRACT

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 Tmax, Cmax 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.