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目的:研究吴茱萸粉末醋调敷日本大耳兔足心后吴茱萸碱(EVO)和吴茱萸次碱(RUT)的药代动力学特征,探讨吴茱萸穴位贴敷疗法的药动学基础。方法:吴茱萸粉末(1.0 g·kg~(-1))醋调敷雄性日本大耳兔足心12 h,于不同时间点(0,1,2,3,4,5,6,8,10,12,24 h)心脏取血,血浆样品用乙腈萃取并沉淀蛋白,采用LC-MS检测血浆中EVO和RUT的血药浓度,采用Phenomenex Gemini C_(18)色谱柱(4.6 mm×150 mm,5μm),流动相乙腈-5 mmol·L~(-1)甲酸铵水溶液(62∶38),流速0.4 mL·min~(-1),柱温25℃,以色胺酮(TRY)为内标,采用电喷雾离子化(ESI)和正离子多离子反应监测(MRM)模式检测。采用PKSolver 2.0软件的非房室模型拟合药动学参数。结果:EVO和RUT的主要药动学参数半衰期(t_(1/2))分别为(18.55±7.98),(20.15±1.06)h;达峰时间(T_(max))分别为5,4 h;药峰浓度(C_(max))分别为(4.68±0.34),(9.76±1.05)μg·L~(-1);药时曲线下面积AUC_(0-t)分别为(58.18±5.46),(155.38±13.91)μg·L~(-1)·h,AUC_(0-∞)分别为(101.46±23.34),(300.32±36.22)μg·L~(-1)·h;平均驻留时间(MRT_(0-∞))分别为(27.63±9.34),(31.25±1.47)h。结论:吴茱萸粉末醋调敷日本大耳兔足心后,EVO和RUT均可透皮吸收入血,且撤药后24 h内仍能维持血药浓度,为吴茱萸穴位贴敷给药提供了实验依据。
Objective: To study the pharmacokinetics of evodiamine and rutaecarpine evodiamine (EVO) and rutaecarpine (RUT) after application of Evodia rutaecarpa powder to the Japanese eared rabbit. Methods: Fructus Evodiae powder (1.0 g · kg ~ (-1)) vinegar was applied to the male Japanese eared rabbit foot hearts for 12 hours at different time points (0,1,2,3,4,5,6,8,10 , 12, 24 h). The plasma samples were extracted with acetonitrile and precipitated. The plasma concentrations of EVO and RUT were detected by LC-MS. Phenomenex Gemini C 18 column (4.6 mm × 150 mm, The mobile phase consisted of acetonitrile-5 mmol·L -1 ammonium formate solution (62:38), the flow rate was 0.4 mL · min -1, the column temperature was 25 ℃ and the tryptamine (TRY) Standard, using electrospray ionization (ESI) and positive ion multi-ion reaction monitoring (MRM) mode detection. Non-compartmental models using PKSolver 2.0 software to fit pharmacokinetic parameters. Results: The half-lives (t 1/2) of the main pharmacokinetic parameters of EVO and RUT were (18.55 ± 7.98) and (20.15 ± 1.06) h, respectively. The peak time (T max) (Cmax) were (4.68 ± 0.34) and (9.76 ± 1.05) μg · L -1, respectively. The area under the curve of drug concentration (AUC_ (0-t) were 58.18 ± 5.46, , (155.38 ± 13.91) μg · L -1 · h -1 and (AUC 0 -∞) were (101.46 ± 23.34) and (300.32 ± 36.22) μg · L -1 · h, respectively. The time (MRT_ (0-∞)) was (27.63 ± 9.34) and (31.25 ± 1.47) h, respectively. CONCLUSION: EVO and RUT can be transdermally absorbed into the blood after evacuation of Evodia rhamnoides powder and application of Evodia rutaecarpa to the blood, and the blood concentration can be maintained within 24 h after evacuation of Evodia. in accordance with.