UPLC-MS/MS法测定大鼠血浆中雷公藤内酯醇及其药代动力学  

A high-sensitivity UPLC-MS/MS determination for triptolide in rat plasma and its pharmacokinetics

作　　者：秦春雨[1] 周滔[1] 宫雯雯[1,2] 白露[1] 秦一[1] 徐唯哲[1] 徐平湘[1,3] 王晓民[2] 薛明[1,3] 

机构地区：[1]首都医科大学基础医学院药理学系,北京100069 [2]首都医科大学基础医学院神经生物学系,北京100069 [3]生物医学检测技术与仪器北京实验室,北京100069

出　　处：《首都医科大学学报》2015年第1期121-126,共6页Journal of Capital Medical University

基　　金：科技部"十二五"国家科技支撑计划资助项目(2011ZX09102-003-01)~~

摘　　要：目的建立大鼠血浆中雷公藤内酯醇的超高效液相色谱质谱联用（ultra performance liquid chromatography-mass spectrometer/mass spectrometer,UPLC-MS/MS）法测定大鼠灌胃给药与静脉注射给药后的血浆药物浓度,并进行药代动力学参数评价。方法 Sprague Dawley大鼠分别经灌胃与尾静脉注射给药,经颈静脉取血,测定不同时间的大鼠血浆药物浓度,并计算其主要药代动力学参数。结果在0.1~200.0 ng/m L质量浓度范围内,血浆雷公藤内酯醇线性关系良好,血浆中雷公藤内酯醇的定量限为0.1 ng/m L,该药稳定性良好,回收率均在95%以上,日内与日间差异均小于15%。口服与静脉给药后,雷公藤内酯醇在大鼠体内的消除均较快,口服生物利用度为9.5%。结论本实验操作简便、稳定可靠、检测限低、效率高、重现性好,可以可靠地用于雷公藤内酯醇血药浓度测定及其药代动力学研究,本研究结果为雷公藤内酯醇的结构优化、剂型改进以及临床应用提供了实验依据。Objective To develop a high-sensitivity liquid chromatographic（ UPLC） assay for determing the triptolide in rats plasma and to study the pharmacokinetics of triptolide in rats. Methods Sprague Dawley rats were given triptolide at the doses of 40 μg/kg and200 μg/kg via oral administration and i. v. administration. The samples of plasma were collected at different times after administration and a ultra performance liquid chromatography-mass spectrometer/mass spectrometer（ UPLC-MS/MS） was developed to determine the concentration of triptolide in biological samples. The plasma samples were extracted by ethylacetate and separated by a C18 reversed-phase column with a cycle time of 4 min. Results The linear range of 0. 1- 200. 0 ng/m L,and lower limits of detection of 0. 05 ng/m L and quantification of 0. 1 ng/m L were established. This method was successfully applied to determine triptolide in rat plasma. The mean recovery was more than 95%. The relative standard deviation（ RSD） of intra-day and inter-day were all less than 15%. After oral administration of triptolide with two dosages（ 40 and 200μg/kg） to rats,the corresponding distribution half-time were 1. 45,3. 05 h,respectively and the half-time of iv administration was 12. 47 min. Conclusion This method is convenient,accurate and reliable. It can be used for determining the triptolide in rats plasma and pharmacokinetic studies.

关 键 词：雷公藤内酯醇 超高效液相色谱-质谱联用法 血药浓度 药代动力学 

分 类 号：R969.9[医药卫生—药理学]