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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: To establish a method for the determination of evodiamine and rutaecarpine in rat plasma by LC-MS and investigate its pharmacokinetics in rats. Methods: The blood samples of Evodia rutaecarpa were collected by gavage at different time points after the administration of Evodia rutaecarpa. The plasma concentrations of test components were determined by LC-MS. Pharmacokinetic parameters were calculated by WinNonlin 5.1 software. Results: Evodiamine and rutaecarpine showed a good linear relationship with 0.5 ~ 100μg.L-1 (r = 0.995 9) and 1 ~ 200μg.L-1 (r = 0.999 3) respectively. The average recovery was more than 76% , Daytime RSDs were less than 15%. After evacuation of Evodia rutaecarpa extract (0.4,0.8,2.4 g · kg-1), evodiamine evoked evodiamine (AUC) 1.144 ± 1.81, 1.117 ± 1.73, 1.177, respectively. The values of t1 / 2 were (146.57 ± 38.38), (114.38 ± 14.65) and (163.37 ± 8.83) 193 224.63 ± 62278.74) mL.min-1. The AUC values of rutaecarpine were (2 283.53 ± 298.51), (4 424.84 ± 276.95) and (14 239.93 ± 3 648.27) min.ng-1. / 2 were (167.10 ± 15.82), (131.58 ± 20.07), (144.41 ± 13.65) min, respectively; CL_F were (1 177 340.54 ± 24942.21), (181 262.92 ± 11 162.22), (177 508.10 ± 52 611.80) mL .min-1. Conclusion: This method is of high specificity and high sensitivity and can be used for quantitative analysis of evodiamine and rutaecarpine in vivo. Evodiamine, rutaecarpine in rats consistent with the primary absorption of a one-compartment model.