Zhang Jun, Liu Shi-Jia, Hu Jie-Hui, Xu Mei-Juan, Liu Zi-Xiu, Zhou Ling, Ju Wen-Zheng
Clinic Pharmacology Laboratory, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
Applied Biosystems SCIEX Co., Ltd., Shanghai 200233, China.
Zhongguo Zhong Yao Za Zhi. 2016 Jul;41(14):2727-2731. doi: 10.4268/cjcmm20161426.
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 C₈ (2.0 mm×50 mm, 3 μm) column with methanol-acetonitrile isopropanol(1∶1)-1‰formic 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 pharmacokinetic 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,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. The established LC-MS/MS method was proved to be sensitive, accurate and convenient, suitable for the pharmacokinetic study of Tripterygium tablet in Beagle dogs.
建立一种测定比格犬血浆中雷公藤红素的液相色谱-串联质谱(LC-MS/MS)方法,并研究雷公藤片口服给药后的药代动力学。血浆样品用二氯甲烷萃取,在Phenomenex Luna C₈(2.0 mm×50 mm,3 μm)色谱柱上分离,以甲醇-乙腈-异丙醇(1∶1)-1‰甲酸(15∶55∶30)为流动相。在多反应监测(MRM)模式下监测雷公藤红素([M+H] ⁺,m/z 451.3/201.1)和内标泼尼松龙([M+H] ⁺,m/z 361.1/147.1)。用药物与统计软件1.0模拟浓度-时间曲线并计算药代动力学参数。雷公藤红素与内标泼尼松龙的峰面积比在0.680 0~136.0 μg•L⁻¹范围内呈良好的线性关系。定量限为0.680 0 μg•L⁻¹,日内和日间精密度均在6.15%以内。绝对回收率在50.42%至51.65%之间。浓度-时间曲线符合一室模型(w=1/cc)。单剂量给药后的主要药代动力学参数如下: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。所建立的LC-MS/MS方法灵敏、准确、简便,适用于比格犬雷公藤片的药代动力学研究。