摘要
目的建立LC／APCI／MS／MS法测定Beagle犬血浆中雷公藤甲素，研究Beagle犬单剂量口服雷公藤片后体内雷公藤甲素药动学。方法血浆样品经乙酸乙酯提取，色谱柱为AgilentZORBAXSBC18（3．0mm×100mm，3．5μm），运用甲醇～醋酸铵缓冲液梯度洗脱，多反应监测（MRM）雷公藤甲素（[M＋H]＋，m／z378．5／361．3）和内标泼尼松龙（[M＋H]＋，m／z361．3／147．0）。Beagle犬单剂量口服雷公藤片（1片／kg）后，采用该方法测定血浆中雷公藤甲素，DAS（1．0）软件对雷公藤甲素药-时曲线进行拟合，并计算药代动力学参数。结果在0．16—20．55μg·L^-1内，雷公藤甲素与内标的峰面积比值与浓度的线性关系良好，日内日间精密度小于6．15％，提取回收率大于79．14％。Beagle犬口服雷公藤片后，雷公藤甲素主要药动学参数为：Cmax／μg·L^-1：2．78±0．387；Tmax／h：1．75±0．76；T1/2／h：2．59±0．60；CL／L·kg^-1·h^-1：2．768±0．606；AUC（0～9）／μg．L^-1．h：11，539±1．491；AUC（0-∞）／μg·L^-1·h：13．185±1．686。结论建立的LC／APCI／MS／MS分析方法准确灵敏，适用于雷公藤片中雷公藤甲素在Beagle犬体内的药代动力学研究。
Aim To establish a LC/APCI/MS/MS method for the determination of triptolide in Beagle plasma, and to investi- gate the pharmaeokinetics of triptolide in tripterygium tablets in Beagle dogs. Methods Plasma samples were prepared by liq- uid-liquid extraction with ethyl acetate. The analytes triptolide and prednisolone（IS） were separated on an Agilent ZORBAX SB C18 column （3.0 mm× 100 mm, 3.5 μm） via gradient elution with methanol and ammonium acetate buffer. Detection of the an- alytes was performed on a tandem MS with multiple-reaction-mo- nitoring mode. The precursor to product ion transitions monitored for triptolide and IS were m/z 378.5→361.3 and 361.3→147. 0, respectively. Afler method validation, this LC/APCI/MS/MS method was applied to determine the plasma concentration of triptolide in Beagle dogs following single oral administration of tripterygiumtablets （ l tablet/kg ）. The concentration-time curveswere simulated with by Drug And Statistic software （1.0） and the pharlnacokinetic parameters were calculated. Results The assay was validated with linear range of 0. 161 - 20.6 μg · L^- 1 tor triptolide. The intra- and inter-batch precisions （RSD%） were within 6. 15%. The absolute recoveries were more than 79. 14% for triptolide. The pharmacokinetic parameters after a single dose were as follows ：Cmax/μg·L^-1：2.78±0.387;Tmax/h：1.75±0.76;T1/2/h：2.59±0.60;CL/L·kg^-1·h^-1：2.768±0.606;AUC（0～9）/μg.L^-1.h：11,539±1.491;AUC（0-∞）/μg·L^-1·h：13.185±1.686. Conclusion The assay method proves to be sensitive, accurate and conven- ient, which can be successfully applied to a pharmacokinetic study of tripterygium tablets in Beagle dogs.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2013年第12期1765-1768,共4页
Chinese Pharmacological Bulletin
基金
国家科技部"重大新药创制"资助项目(No 2012ZX09303009-002)
江苏省中医药领军人才(No LJ200906)
