摘要
目的 建立人肝微粒体中西尼地平及其脱氢代谢物的 HPLC测定法 ,并用本法研究西尼地平在人肝微粒体中代谢的动力学。方法 色谱柱为 Hypersil C1 8柱 (2 5 0 mm× 4.6mm ID,5μm) ,流动相为乙腈 -甲醇 -0 .0 1 mol/ L四丁基溴化铵溶液 (5 5∶ 5∶ 40 ,V/ V/ V) ,柱温 5 0℃ ,检测波长 UV 2 3 8nm,样品用乙醚 -正己烷 (1∶ 1 ,V/ V)提取。用人肝微粒体研究西尼地平的代谢。结果 本法的回收率为 90 .62 %～ 1 0 9.90 % ,西尼地平和其脱氢代谢物的日间、日内 RSD分别为 4.70 %～ 8.3 5 %和 3 .88%～ 8.1 1 % ,西尼地平及其脱氢代谢物的浓度分别在 0 .77μg/ ml～ 98.2 4μg/ ml和 0 .1 3 μg/ ml～ 5 .3 6μg/ ml范围内与峰面积呈良好的线性相关性。在温孵时间为1 0～ 60 min,微粒体蛋白浓度为 1 mg/ ml时 ,西尼地平呈线性消除 ,而其脱氢代谢物呈线性增加。结论 西尼地平在人肝微粒体内被迅速代谢 ,人肝 P45
AIM A HPLC method for the determination of cilnidipine and its major metabolite was developed and the kinetics of its metabolism in human liver microsomes was studied. METHODS Chromatography was performed on an Hypersil BDS C 18 column. An acetonitril methanol water containing 0.01 mol/L tetrabutyl ammonium bromide(55∶5∶40,V/V/V) as the mobile phase was used with the UV detector set at 238 nm. Following alkalinization with NaOH, human liver microsomes were extracted with n hexane ether(1∶1,V/V). RESULTS The recovery of cilnidipine and its major metabolite for the proposed method was more than 90%. The relative standard deviations for within day and between day were 4.70%~8.35% for cilnidipine, and 3.88% 8.11% for its major metabolite. The calibration curve was linear in the range from 0.77 μg/ml to 98.24 μg/ml with r =0.999 for cilnidipine and from 0.13 μg/ml to 5.36 μg/ml with r =0.999 for its major metabolite. The elimination of cilnidipine and the formation of the metabolite was linear. CONCLUSION Cilnidipine was rapidly metabolized in human liver microsomes and three metabolites of cilnidipine were isolated. The results suggested that CYP450 was involved in the metabolism of cilnidipine.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2002年第4期304-307,共4页
Journal of China Pharmaceutical University
基金
国家自然科学基金 (3 9970 862 )
国家 973基金 (G19980 5 1119)资助项目
