Beagle犬口服雷公藤片血浆中雷公藤红素LC-MS/MS测定及药动学研究  

LC-MS/MS method for determination of tripterine in plasma:pharmacokinetic study in Beagles

作　　者：张军[1] 刘史佳[1] 胡杰慧 许美娟[1] 刘子修[3] 周玲[3] 居文政[1] 

机构地区：[1]南京中医药大学附属医院临床药理科,江苏南京210029 [2]ABSCIEX公司,上海200233 [3]南京中医药大学,江苏南京210002

出　　处：《中国中药杂志》2016年第14期2727-2731,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金青年基金项目(81403174);江苏省自然科学基金面上项目(BK20151602)

摘　　要：建立Beagle犬血浆中雷公藤红素的LC-MS/MS检测方法,用于Beagle犬口服雷公藤片的药代动力学研究。血浆样品经二氯甲烷提取,色谱条件为Phenomenex Luna C8色谱柱(2.0 mm×50 mm,3μm),流动相为甲醇-乙腈异丙醇溶液(1∶1)-0.1%甲酸15∶55∶30;多反应监测(MRM)雷公藤红素([M+H]+,m/z 451.3/201.1)和内标泼尼松龙([M+H]+,m/z 361.1/147.1);DAS 1.0软件对雷公藤红素药-时曲线进行拟合,并计算药代动力学参数。在0.680 0~136.0μg·L-1,雷公藤红素与内标的峰面积比值与浓度的线性关系良好,定量限为0.680 0μg·L·(-1),日内日间精密度小于6.15%,提取回收率为50.42%~51.65%。Beagle犬口服雷公藤片(1片/kg),血浆中雷公藤红素经时变化符合一室模型(w=1/cc),主要药动学参数分别为Cmax(35.64±9.540)μg·L^(-1),Tmax(2.62±0.69)h,T1/2(2.93±0.29)h,CL(0.308±0.056)L·kg^(-1)·h^(-1),AUC0-12(131.16±31.94)μg·L·h^(-1),AUC0-∞(142.83±37.57)μg·L·h^(-1)。建立的LC-MS/MS分析方法准确灵敏,适于雷公藤片中雷公藤红素药代动力学研究。To establish a LC-MS/MS method for determination of tripterine in Beagle plasma and study its pharmacokinetics after oral administration of tripterygium tablet. Plasma samples were extracted with dichloromethane and separated on a Phenomenex Luna Cs （2. 0 mm x50 mm, 3 Ixm） column with methanol-acetonitrile isopropanol（ 1：1 ）-1%dormic acid （ 15：55 ： 30） as the mobile phase. Tripterine （ [ M ＋ H]＋ , m/z 451.3/201.1 ） and internal standard prednisolone （ [ M ＋ H]＋ , m/z 361.1/147. 1 ） were monitored in multiple reaction monitoring （MRM）. The concentration-time curves were simulated by drug and statistic software 1.0 and the pharma- cokinetic parameters were calculated. There was a good linear relationship between peak area ratio and concentration of tripterine and internal standard prednisolone within range of 0. 680 0-136. 0 μg·L-1. The limit of quantitation was 0. 680 0 μg·L-1 and the intra- and inter-day precision was within 6. 15%. The absolute recovery rate was between 50. 42% to 51.65%. The concentration-time curves were consistent with the one-compartment model（w = 1/cc）. The main pharmacokinetic parameters after a single dose were as follows： Cmax （ 35.64 ± 9. 540） μg·L-1 Tmax （2. 62 ± 0. 69 ） h, TI/2 （2. 93± 0. 29） h, CL （0. 308 ± 0. 056） L kg-1 h -1, AUC0.12 （ 131.16 ±31.94） μg·L-1 h-1, AUC0-∝ （ 142. 83±37.57） μg·L-1 h-l. The established LC-MS/MS method was proved to be sen-sitive, accurate and convenient, suitable for the pharmacokinetic study of Tripterygium tablet in Beagle dogs.

关 键 词：雷公藤红素 雷公藤片 高效液相色谱-质谱联用 药代动力学 

分 类 号：R285.5[医药卫生—中药学] O657.63[医药卫生—中医学]