LC-MS方法研究氢溴酸高乌甲素在小鼠体内的药代动力学(英文)  

Pharmacokinetic study of lappaconitine hydrobromide in mice by LC-MS

作　　者：汪晴[1] 李子敬[1] 孙璐[2] 高丽英[2] 李明慧[1] 郝佳佳[1] 张欣[1] 孙玉明[1] 

机构地区：[1]大连理工大学制药科学与技术学院,辽宁大连116024 [2]沈阳药科大学药学院,辽宁沈阳116016

出　　处：《药学学报》2011年第4期432-437,共6页Acta Pharmaceutica Sinica

基　　金：Project supported by Ministry of Science and Technology of China Eleventh 5-year Plan-Technical Platform for drug Development(No.2009ZX09502)

摘　　要：本文建立了一种快速、灵敏的LC-MS法用于检测小鼠血浆中的高乌甲素浓度。采用ESI源和多反应监测(MRM)的方式进行检测,所选用的高乌甲素和内标延胡索乙素的反应离子对分别为m/z 585→535和m/z 356→m/z 192。该方法在3.0～2 000.0 ng·mL-1浓度内线性关系良好,定量下限为3.0 ng·mL-1,日内和日间精密度(RSD)均小于9.9%,准确度(RE)在±4.8%之内。氢溴酸高乌甲素分别以1.0、2.0和4.0 mg·kg-1单剂量静脉注射给予小鼠后,t1/2分别为0.47、0.48和0.49 h,AUC0-t分别为55.5、110.5和402.9 ng·h·mL-1。实验结果表明,氢溴酸高乌甲素单剂量静脉注射给予小鼠后,在低剂量(1.0～2.0 mg·kg-1)范围内其药动学行为符合线性动力学特征,当给药剂量(2.0 mg·kg-1)增大至4.0 mg·kg-1时,AUC增加至约4倍,而Vz和CL却显著降低,呈现非线性动力学特征,可能与高浓度下药物血浆蛋白结合率的降低有关。A high sensitive and rapid method was developed for the analysis of lappaconitine in mouse plasma using liquid chromatography coupled to mass spectrometry（LC-MS）.Detection was performed by positive ion electrospray ionization（ESI） in multiple reaction monitoring（MRM） mode,monitoring the transitions m/z 585 → m/z 535 and m/z 356 → m/z 192,for the quantification of lappaconitine and tetrahydropalmatine（internal standard,IS）,respectively.The method was linear over the concentration range of 3.0-2 000.0 ng·mL-1.The lower limit of quantification was 3.0 ng·mL-1.Intra-and inter-run precisions（RSD） were both less than 9.9% and accuracy（RE） within ± 4.8%.After single intravenous injections of lappaconitine hydrobromide at 1.0,2.0 and 4.0 mg·kg-1,the elimination half-lives（t1/2） were 0.47,0.48 and 0.49 h,and the areas under the curve（AUC0-t） were 55.5,110.5 and 402.9 ng.h.mL-1,separately.The pharmacokinetic profile of lappaconitine was linear at relatively lower dose levels（1.0-2.0 mg·kg-1）.When the dose increased farther to 4.0 mg·kg-1,the Vz and CL decreased,and the increase fold of the AUC was much larger than that of the dose.

关 键 词：氢溴酸高乌甲素 HPLC-MS 药代动力学 

分 类 号：R917[医药卫生—药物分析学]