作者：简锐, 廖昌军, 张全, 周爱民, 何阳森
作者单位：成都医学院药学院，四川 成都 610083
关键词：雷公藤甲素;液质联用;药代动力学;温敏凝胶
摘要：
建立LC-MS测定雷公藤甲素（TP）在大鼠体内血药浓度方法，并计算药代动力学参数。采用Agilent ZORBAX SB-C18(2.1 mm×50 mm，1.8 μm)色谱柱；流动相为甲醇(A)-水溶液(B)梯度洗脱；流量为0.3 mL/min；柱温35 ℃；进样量5 μL；多反应监测(MRM)，离子化方式为负模式。SPF级SD大鼠18只，分为空白、温敏凝胶和溶液组，采用单剂量关节腔注射给药。给药后大鼠尾部静脉取血，LC-MS测定各时间点血浆药物浓度，DAS3.0计算药代动力学参数。在0.1~2.0 μg/L浓度范围内，TP与内标阿魏酸峰面积比值与浓度的线性关系良好。温敏凝胶和溶液组主要药动力学参数t1/2、Tmax和AUC分别为：27.506 h、0.75 h、3.972 μg/L·h和16.967 h、0.5 h、2.283 μg/L·h。该方法可用于TP关节腔注射给药在大鼠体内药代动力学研究，为TP温敏凝胶制剂开发提供理论依据。
Research on pharmacokinetic of triptolide thermosensitive gel for rats
JIAN Rui, LIAO Changjun, ZHANG Quan, ZHOU Aiming, HE Yangsen
School of Pharmacy, Chengdu Medical College, Chengdu 610083, China
Abstract: This paper established a LC-MS method for determining the plasma concentration of triptolide (TP) in rats and to calculate pharmacokinetic parameters. An Agilent ZORBAX SB-C18 (2.1 mm×50 mm, 1.8 μm) chromatographic column was used; the mobile phase was methanol (A)-aqueous solution (B) gradient elution; the flow rate was 0.3 mL/min; the column temperature was 35 ℃ ; the injection volume 5 μL; Multiple Reaction Monitoring (MRM), ionization mode was negative mode. 18 SPF grade SD rats were divided into blank, temperature-sensitive gel and solution groups, and were administered by single-dose intra-articular injection. After administration, blood was collected from the tail vein of rats, and the plasma drug concentration was determined by LC-MS at each time point. DAS3.0 was used to calculate the pharmacokinetic parameters. Within the concentration range of 0.1-2.0 μg/L, the linear relationship between the ratio of TP and internal standard ferulic acid peak area and concentration was good. The main pharmacokinetic parameters t1/2, Tmax and AUC of the temperature-sensitive gel and solution groups were: 27.506 h, 0.75 h, 3.972 μg/L·h and 16.967 h, 0.5 h, 2.283 μg/L·h. This method can be used to study the pharmacokinetics of TP articular injection in rats, and provided a theoretical basis for the development of TP temperature-sensitive gel formulations.
Keywords: triptolide;LC-MS;pharmacokinetics;thermosensitive gel
2020, 46(11):48-52 收稿日期: 2020-04-18;收到修改稿日期: 2020-05-23
基金项目: 国家自然科学基金项目（81603045）
作者简介: 简锐(1996-),女,四川泸州市人,硕士研究生,专业方向为工业药剂学方向
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