手性固定相HPLC法测定大鼠血浆阿罗洛尔对映体及药代动力学研究  

In vivo determination and pharmacokinetics analysis of arotinolol enantiomers in Wistar rats

作　　者：许艳海 陈朗东 方俊聪 郑乐艺 张劲柏[1] 闻俊[1] 洪战英[1] 柴逸峰[1] 范国荣[1] 

机构地区：[1]第二军医大学药学院,上海市药物(中药)代谢产物研究重点实验室 [2]中国人民解放军69339部队 [3]中国人民解放军96123部队

出　　处：《药物分析杂志》2015年第9期1539-1543,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：第二军医大学大学生创新科研重点项目(ZD2013026)

摘　　要：目的：建立大鼠血浆中阿罗洛尔对映体的HPLC定量分析方法,并研究盐酸阿罗洛尔片在Wistar大鼠体内的手性药代动力学特征。方法：血浆样品采用液-液萃取的方法进行前处理。采用Chiralpak AD-H（250 mm×4.6 mm,5μm）手性色谱柱,正己烷-乙醇-二乙胺-三乙胺（30∶70∶0.1∶0.1）为流动相,流速0.4 m L·min-1,检测波长315 nm。结果：d-阿罗洛尔和l-阿罗洛尔质量浓度均在0.025~1.25μg·m L^-1范围内线性关系良好（r^2〉0.99）。阿罗洛尔对映体的回收率均大于94.1%,日内、日间RSD均小于15%。应用本文方法测定Wistar大鼠灌胃给药阿罗洛尔后的各对映体血浆浓度,获得相应的药动学参数,d-阿罗洛尔和l-阿罗洛尔的Cmax、AUC0-∞分别为0.225μg·m L^-1、1.82μg·h·m L^-1和0.226μg·m L^-1、1.84μg·h·m L^-1。结论：该方法经方法学验证,可用于阿罗洛尔对映体在大鼠体内药代动力学研究,发现阿罗洛尔对映体在大鼠血浆药动学特征不存在立体选择性。Objective： To establish a method for the determination of arotinolol enantiomers in rat plasma,and to study its pharmacokinetic features in Wistar rats. Methods： The plasma samples were pretreated with liquid-liquid extraction. The concentrations of arotinolol enantiomers in rat plasma were determined by HPLC with Chiralpak AD-H column（ 250 mm × 4. 6 mm,5 μm） and UV detector. The mobile phase consisted of hexane-ethanol-diethylamine-triethylamine（ 30∶ 70∶ 0. 1 ∶ 0. 1）,with a flow rate of 0. 4 m L·min- 1. The detection wavelength was set at 315 nm. Results： Good linear relationship was obtained in the range of 0. 025-1. 25 μg·m L^-1（ r^2〉0. 99）.The recoveries of arotinolol enantiomers were above 94. 1%. The intra-day and inter-day RSD for arotinolol were lower than 15%. After intragastric administration,the Cmaxand AUC0- ∞of d-arotinolol were 0. 225 μg·m L^-1and1. 82 μg·h·m L^-1,respectively. The Cmaxand AUC0- ∞of l-arotinolol were 0. 226 μg·m L^-1and 1. 84 μg·h·m L^-1,respectively. Conclusion： The established method is proved suitable for the pharmacokinetic study of arotinolol in Wistar rats. In addition,our results indicate that arotinolol enantiomers have no chiral selectivity in Wistar rats.

关 键 词：阿罗洛尔 手性药物检测 对映体 手性固定相 液-液萃取 药代动力学 高效液相色谱 

分 类 号：R917[医药卫生—药物分析学]