LC-MS法测定Beagle犬血浆中人参皂苷20(R)-Rh_2及其药代动力学研究  

Pharmacokinetic study of ginsenoside 20(R)-Rh_2 in Beagle dogs by LC-ESI-MS

作　　者：顾轶[1] 王广基[1] 孙建国[1] 谢海棠[1] 贾元威[1] 许美娟[1] 吕华[1] 黄晨蓉 王玮[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室

出　　处：《中国临床药理学与治疗学》2006年第3期256-260,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家"863"计划基金资助项目(№2003AA2Z347A);国家自然科学基金资助项目(№305722228);江苏省自然科学基金资助项目(№BK2005098)

摘　　要：目的：建立测定人参皂苷20（R）-Rh2血浆药物浓度的液相色谱．电喷雾离子化．质谱联用的分析方法（LC-ESI-MS），探讨其在Beagle犬体内的药代动力学研究中的应用。方法：Beagle犬6只，随机分为2组，采用单剂量双周期自身交叉设计，分别给犬单剂量静注（0．1mg·kg^-1）或灌胃（1mg·kg^-1）20（R）-Rh2，用LC-MS法测定给药后的血浆中药物浓度，计算其药代动力学参数，以及在Beagle犬体内的绝对生物利用度。结果：20（R）．Rh2在0.5～200ng·ml^-1浓度范围内线性关系良好（r^2=0．9998），样品在血浆中的提取回收率大于70％，批内和批间的RSD均小于15％，静注后主要药代动力学参数T1/2，CL，AUC 0-∞ 分别为8．0±2．8h、0．1±0．03L·kg^-1·h、857．0±209．6ng·h·ml^-1；口服后主要药代动力学参数Tmax，Cmax，T1-2，AUC0-∞分别为2．6±1．3h、371．0±199．6ng·ml^-1。、5．8±2．6h、1215．7±598．6ng·h·ml^-1。绝对生物利用度为（16．1±11．3）％。结论：该法专属性强，灵敏度高，可用于20（R）-Rh2的体内定量分析。人参皂苷20（R）-Rh2在Beagle犬体内的绝对生物利用度较低。ABSTRACT AIM： To establish an LC-ESI-MS method for determination of ginsenoside 20（ R）-Rh2 and investigate its application to pharmacokinetic and absolute bioavailability study in Beagle dogs. METHODS： According to a randomized two-peried crossover design, beagle dogs were given 1 and 0.1 mg.kg-I 20（R）-Rh2 via po and iv respectively. Drug plasma concentration was determined by LC-ESI-MS. Pharmaeokinetie parameters were evaluated and absolute bioavailability was also calculated. RESULTS： The methed was linear over the range of 0.5200 ng-ml^-l （R2 = 0.9998）;The recovery of 20（R）-Rh2 in dog plasma was more than 70 % ; Intra and interbatch precision, expressed as the relative standard （RSD） was less than 15% ; After iv administration of 20（R）-Rh2, the main pharmacokinetic parameters T1-2, CL, AUC0-∞ were 8.0 ± 2.8 h,0.1 ± 0.03 L.kg^-1.h^-1, 857.0 ± 209.6 ng. h. ml^-1 respectively; after po administration, the major pharmaeokinetic parameters Tmax, Cmax, T1-2, AUC0-∞ were 2.6 ± 1.3 h, 371.0 ±199.6 ng.ml^-1 ,5.8 ± 2.6 h, 1215.7 ± 598.6 ng.h.ml^-1 respectively. The absolute bioavailability was 16.1% ± 11.3 % after the correction of dosage. CONCLUSION： The method described in this report was sensitive and specific, and suitable for pharmaeokinetie studies of 20 （ R）Rh2 in dog. The absolute bioavailability of 20（R）-Rh2 in dog was relative low.

关 键 词：人参皂苷20(R)-Rh2 液相色谱-电喷雾离子化-质谱联用法 药代动力学 绝对生物利用度 

分 类 号：R969.1[医药卫生—药理学]