香附四物汤全方及其效应部位中3个生物碱类成分在比格犬体内的药动学比较研究  

Comparative study on pharmacokinetics in Beagle dog plasma of three major alkaloids of Xiangfusiwu decoction and its active fraction

作　　者：李振皓[1] 刘培[1] 钱大玮[1] 段金廒[1] 李炜[1] 钱叶飞[1] 尚尔鑫[1] 唐于平[1] 

机构地区：[1]南京中医药大学江苏省方剂高技术研究重点实验室,南京210046

出　　处：《药物分析杂志》2013年第3期355-361,共7页Chinese Journal of Pharmaceutical Analysis

基　　金：江苏省高校自然科学重大基础研究项目(06KJA36022);南京中医药大学方剂重点学科资助项目(2011FJ006)

摘　　要：目的:研究香附四物汤全方水提液(QF)及其效应部位(BW)中3个生物碱类成分经口服给药后药物代谢动力学特征的差异。方法:采集比格犬灌胃QF及BW后不同时间点的血浆样本,采用LC-MS/MS以多反应离子监测(MRM)方式进行正离子检测,测定血浆中普鲁托品、延胡索乙素、四氢非洲防己碱的浓度,DAS软件计算主要药动学参数。结果:普鲁托品在QF与BW中的各项参数除Cmax外差异没有统计学意义,BW中Cmax大于QF(P<0.05);延胡索乙素在体内消除缓慢,QF和BW均出现了双峰现象,QF中Tmax、AUC0～T与BW相比明显增大(P<0.05);四氢非洲防己碱达峰较快,BW中Cmax大于QF(P<0.05)。结论:QF和BW药动学参数的差异有统计学意义,提示两者的差异成分会对普鲁托品、延胡索乙素和四氢非洲防己碱的体内过程产生影响。Objective ： To establish an LC - MS/MS method to determine the plasma concentration of protopine, tet- rahydropalmatine and tetrahydrocolumbamine in Beagle dogs, and to compare the pharmacoknetic parameters of three alkaloids of Xiangfusiwu decoction and its active fraction in Beagle dogs after oral administration. Methods： Electrospray ionization （ESI）source was applied and operated in the positive ion mode. Multiple reaction monitoring （MRM） mode with the transitions of m/z 354→m/z 188 for protopine, m/z 356→m/z 192 for tetrahydropalmatine and m/z 342→m/z 178 for tetrahydrocolumbamine was used to quantify three alkaloids. The blood samples were collected at different time points after the Xiangfusiwu decoction and its active fraction were orally administrated. The plasma concentration of three alkaloids was then detected by LC - MS/MS. The pharmacoknetic parameters were calculated by DAS 2.0 program. Results： The pharmacokinetic parameters of protopine of the decoction and fraction showed certain difference, but there was no significant difference on parameters except Cmax among the de- coction and fraction;The elimination of tetrahydropalmatine was slow, double peaks were observed in both decoction and fraction, and Tmax, AUC0-Tr of decoction remarkably increased compared with those of fraction （P 〈 0.05 ） ; TmaxOf tetrahydrocolumbamine was short, and Cmax of the decoction and fraction showed significant difference （ P 〈 0.05 ）. Conclusion： The method used was sensitive, selective, rapid and successfully applied to a pharmacokinetic study of protopine, tetrahydropalmatine and tetrahydrocolumbamine in Beagle dogs after oral administration of Xiangfusiwudecoction and its active fraction. The pharmacokinetic parameters of the decoction and the fraction showed statistical difference, which suggested that the different components in the decoction could affect the pharmacokinetic parameters of three alkaloids.

关 键 词：香附四物汤 生物碱 普鲁托品 延胡索乙素 四氢非洲防己碱 药代动力学 液质联用 

分 类 号：R917[医药卫生—药物分析学]