Shao Feng, Wang Guang-Ji, Sun Jian-Guo, Xie Hai-Tang, Zhang Rong, Zhu Xiao-Yan
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Yao Xue Xue Bao. 2007 Jan;42(1):61-5.
The aim of this paper is to develop and validate a rapid and sensitive LC-APCI/MS method for the determination of triptolide (TP) in plasma and to study the pharmacokinetic properties of TP in Beagle dogs. Sample preparation consisted of liquid-liquid extraction of interests. with ethyl acetate from dog plasma. The analytes and internal standard prednisolone were well separated on a Zorbax Extend-C18 analytical column. Plasma TP was detected by selected-ion monitoring (SIM) of LC-APCI/MS as its deprotonated molecular ions [M - H] - at m/z 358.9. Pharmacokinetic studies were undertaken in dogs following an iv dose of 0.05 mg x kg(-1) of TP or an ig dose of 0.05, 0.08, 0.1 mg x kg(-1), separately. The pharmacokinetic parameters were calculated by DAS software. Calibration curves were linear over the concentration range of 1 - 200 ng x mL(-1) of TP with the within- and between-batch precisions less than 10%. The within and between-batch accuracy was 95.0% to 105.0%. Recovery of LC-MS method for TP in plasma was over 75%. The T1/2beta was (2.5 +/- 0.8) h after intravenous administration of TP at the dose of 0.05 mg x kg(-1). There were no significant differences in T(max), T1/2 alpha and T1/2 beta among the three ig dosage groups. AUC and C(max) increased proportionally with doses. The absolute bioavailability of TP after ig administration of 0.05 mg x kg(-1) was (75 +/- 17)%. The LC-MS method for determination of triptolide in dog plasma was sensitive and rapid. It was showed that the elimination of triptolide was rapid. The absolute bioavailability of triptolide given orally was high.
本文旨在建立并验证一种快速、灵敏的液相色谱-大气压化学电离/质谱法（LC-APCI/MS）用于测定血浆中雷公藤甲素（TP），并研究TP在比格犬体内的药代动力学性质。样品制备采用液-液萃取法，用乙酸乙酯从犬血浆中提取目标物。分析物和内标泼尼松龙在Zorbax Extend-C18分析柱上分离良好。通过LC-APCI/MS的选择离子监测（SIM）模式，以m/z 358.9处的去质子化分子离子[M - H]-检测血浆中的TP。分别对犬静脉注射0.05 mg·kg-1的TP或灌胃给予0.05、0.08、0.1 mg·kg-1的TP后进行药代动力学研究。药代动力学参数用DAS软件计算。TP浓度在1 - 200 ng·mL-1范围内，校准曲线呈线性，批内和批间精密度均小于10%。批内和批间准确度为95.0%至105.0%。血浆中TP的LC-MS方法回收率超过75%。静脉注射0.05 mg·kg-1的TP后，T1/2β为(2.5 ± 0.8) h。三个灌胃剂量组之间的T(max)、T1/2α和T1/2β无显著差异。AUC和C(max)随剂量成比例增加。灌胃给予0.05 mg·kg-1的TP后，其绝对生物利用度为(75 ± 17)%。用于测定犬血浆中雷公藤甲素的LC-MS方法灵敏且快速。结果表明雷公藤甲素消除迅速，口服给药的绝对生物利用度较高。
