LC-MS测定制吴茱萸提取物中吴茱萸碱、吴茱萸次碱在大鼠体内的药动学  

Studies on pharmacokinetics of evodiamine and rutaecarpine in rats plasma after oral administration extracts of Euodiae Fructus

作　　者：鲍天冬 李玉洁[2] 翁小刚[2] 杨庆[2] 张英丰[2] 董宇[2] 朱晓新[2] 

机构地区：[1]江西济民可信医药有限公司,江西南昌330096 [2]中国中医科学院中药研究所,北京100700

出　　处：《中国中药杂志》2011年第24期3519-3522,共4页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金重点项目(30930114);国家"十一五"科技支撑计划项目(2006BAI08B04-4);国家"重大新药创制"科技重大专项(2009ZX09301-005-09);中国中医科学院自主选题项目(ZZ20090212)

摘　　要：目的:建立LC-MS测定大鼠血浆中吴茱萸碱、吴茱萸次碱含量的方法,并探讨其在大鼠体内的药动学过程。方法:大鼠灌胃制吴茱萸提取物后不同时间点采血,LC-MS测定受试成分血药浓度,并用WinNonlin 5.1软件计算药动学参数。结果:吴茱萸碱、吴茱萸次碱分别在0.5～100μg.L-1(r=0.995 9)和1～200μg.L-1(r=0.999 3)线性关系良好,平均回收率均大于76%,日内、日间RSD均小于15%。大鼠灌胃制吴茱萸提取物0.4,0.8,2.4 g.kg-1后,吴茱萸碱AUC分别为(2 215.24±414.49),(4 230.62±753.77),(13 219.21±3 740.95)min.ng-1.mL-1;t1/2分别为(146.57±38.38),(114.38±14.65),(163.37±8.83)min;CL_F分别为(184 607.29±32 502.21),(192 878.22±31 897.37),(193 224.63±62278.74)mL.min-1;吴茱萸次碱的AUC分别为(2 283.53±298.51),(4 424.84±276.95),(14 239.93±3 648.27)min.ng-1.mL-1;t1/2分别为(167.10±15.82),(131.58±20.07),(144.41±13.65)min;CL_F分别为(1 177 340.54±24942.21),(181 262.92±11 162.22),(177 508.10±52 611.80)mL.min-1。结论:本法专属性强,灵敏度高,可用于吴茱萸碱、吴茱萸次碱的体内定量分析。吴茱萸碱、吴茱萸次碱在大鼠体内符合一级吸收的一室模型。Objective： Develop an LC-MS method to determine evodiamine and rutaecarpine in rats plasma simultaneously.The method was employed to investigate pharmacokinetics of evodiamine and rutaecarpine.Method： Blood samples were collected in different time after oral administrated with the extracts of Euodiae Fructus,the plasma concentration of evodiamine and rutaecarpine was determined by LC-MS,pharmacokinetic parameters were calculated by WinNonlin 5.1 software.Result： The linear ranges of evodiamine and rutaecarpine were 0.5-100 μg·L-1（r=0.995 9）,1-200 μg·L-1（r=0.999 3） respectively.The average recovery were exceeded 76%（n=5）,the precision of inner-day and inter-day were less than 15%.The pharmacokinetics parameters AUC,t1/2,CL_F of evodiamine were：（2 215.24±414.49）,（4 230.62±753.77）,（13 219.21±3 740.95） min·ng-1·mL-1;（146.57 ±38.38）,（114.38 ±14.65）,（163.37 ±8.83） min;（184 607.29 ±32 502.21）,（192 878.22 ±31 897.37）,（19 3224.63 ±62 278.74） mL·min-1.The pharmacokinetics parameters AUC,t1/2,CL_F of rutaecarpine were（2 283.53±298.51）,（4 424.84±276.95）,（14 239.93 ±3648.27） min·ng-1·mL-1;（167.10±15.82）,（131.58±20.07）,（144.41±13.65） min;（1 177 340.54±2 4942.21）,（181 262.92±11 162.22）,（177 508.10 ± 52 611.80） mL·min-1.Conclusion： The method described in this report has high sensitivity and selectivity,and was suitable for pharmacokinetic studies of evodiamine and rutaecarpine.The kinetic process of evodiamine and rutaecarpine in rats in vivo were all yielded to be one-compartment model.

关 键 词：LC-MS 制吴茱萸提取物 吴茱萸碱 吴茱萸次碱 药动学 

分 类 号：R284[医药卫生—中药学]