HPLC法测定Beagle犬血浆中冬凌草乙素浓度及药动学研究  

Determination of plasma ponicidin concentration by HPLC and its pharmacokinetic study in Beagle dogs

作　　者：李晓天[1] 石迎迎[1] 杜斌[2] 褚延乐[1] 王琳茜[1] 于彤[1] 

机构地区：[1]郑州大学药学院,郑州450001 [2]吉林大学药学院,长春130021

出　　处：《中国新药杂志》2013年第10期1214-1217,1227,共5页Chinese Journal of New Drugs

摘　　要：目的:建立一种简便、快速、专属性好、选择性强的HPLC分析方法,测定Beagle犬血浆中冬凌草乙素的浓度,研究其药动学行为。方法:采用HPLC法测定Beagle犬静脉注射给药后不同时间血浆中冬凌草乙素的浓度;Zorbax Eclipse XDB C18柱分离(150 mm×4.6 mm,5μm);流动相为甲醇-磷酸盐缓冲液(pH6.0)(34∶66);流速为1.0 mL.min-1,进样量为20μL;紫外检测波长为232 nm;以非那西丁为内标,乙酸乙酯-异丙醇(95∶5)作为萃取剂。结果:本方法测定冬凌草乙素在20.0～4 000 ng.mL-1浓度范围内呈良好的线性关系,定量下限达20.0 ng.mL-1。日内、日间精密度及准确度均符合生物样品分析要求,RSD均在15%以内,提取回收率大于85%。Beagle犬静脉注射给药后,主要药动学参数t1/2,AUC0～t,AUC0～∞,CL分别为6.47 h,2 294 ng.h.mL-1,2 818 ng.h.mL-1,0.192 mL.kg-1.h-1。结论:本分析方法操作简便、专属性强、可行性高,可用于冬凌草乙素在Beagle犬体内的药动学研究。冬凌草乙素在Beagle犬体内呈二室模型,吸收迅速,消除相对较快。Objective：To establish a simple,rapid, specific and selective HPLC analysis method for deter- mination of ponicidin in Beagle dog plasma and to study its pharmacokinetic properties. Methods：The concentra- tions of ponicidin in the plasma of Beagle dogs were determined by HPLC with Zorbax Eclipse XDB C18 column （ 150 mm × 4.6 mm,5 μm） and UV detector. The mobile phase consisted of methanol-phosphate buffer（pH 6.0） （34： 66）with the flow rate of 1.0 mL-min-1. The injection volume was 20 μL and the detection wavelength was set at 232 rim. Phenacetin was selected as the internal standard and ethyl acetate-isopropyl alcohol（95： 5）was used as the extractant. Results ： The calibration curve showed good linearity in the range of 20.0 - 4 000 ng· mL- 1 and the lower limit of quantification was 20.0 ng. mL-1. The intra-day and inter-day precisions （RSD） were in line with the requirement for analysis of biological samples. The RSDs were less than 15% , and the extraction recoveries were greater than 85%. After intravenous injection, the main pharmacokinetic parameters t1/2, AUC0-1, AUC0 0-∞ , and CL were 6.47 h,2 294 ng·h·mL-1,2 818 ng·h·mL-1 ,and 0. 192 mL-kg-1·h -1, respectively. Conclusion：This anal- ysis method is simple, specific, feasible,and suitable for the pharmacokinetic study of ponicidin in Beagle dogs. The concentration-time curve of ponicidin was fitted to two-compartment model, and ponicidin was absorbed quickly and eliminated relatively fast in Beagle dogs.

关 键 词：冬凌草乙素 HPLC 血药浓度 BEAGLE犬 药动学 

分 类 号：R969.1[医药卫生—药理学] R286.91[医药卫生—药学]