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

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C_max外差异没有统计学意义,BW中C_max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T_max、AUC_0~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_{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,tetrahydropalmatine 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 C_max among the decoction and fraction;The elimination of tetrahydropalmatine was slow,double peaks were observed in both decoction and fraction,and T_max,AUC_0~T of decoction remarkably increased compared with those of fraction(P<0.05); T_max of tetrahydrocolumbamine was short,and C_max 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 Xiangfusiwu decoction 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