在体皮肤微透析技术和HPLC测定吴茱萸碱和吴茱萸次碱的透皮释药特性

目的考察大鼠皮下组织吴茱萸提取物中吴茱萸碱和吴茱萸次碱的含量,评价其透皮释药特性。方法大鼠腹部脱毛,覆盖黑色聚乙烯薄膜经皮给予吴茱萸提取物,应用微透析采样技术结合高效液相色谱法测定大鼠皮下组织中吴茱萸碱和吴茱萸次碱浓度随时间变化的影响。结果透析液中吴茱萸碱最大药物浓度(ρmax)为(417.24±43.44)μg·m L-1,达峰时间(tmax)为(4.210±0.630)h,药-时曲线下面积(AUC0→20)为(3 189.31±789.97)μg·h·m L-1;吴茱萸次碱最大药物浓度(ρmax)为(287.13±26.78)μg·m L-1,达峰时间(tmax)为(3.980±0.580)h,药-时曲线下面积(AUC0→16)为(1 327.97±245.87)μg·h·m L-1。结论在体微透析采样技术结合高效液相色谱法可用于吴茱萸碱和吴茱萸次碱透皮释药特性的评价,方法操作简便、灵敏度高、专属性强。吴茱萸提取物中吴茱萸碱和吴茱萸次碱具有缓慢透皮、渗透量高的特点。

In Vivo Evaluation of Transdermal Delivery Properties of Evodiamine and Rutacarpine by Skin Microdialysis and HPLC Method

OBJECTIVE To determine the concentrations of evodiamine and rutacarpine in subcutaneous tissues of rats after administration of evodiae extract to evaluate the transdermal drug release properties. METHODS The rats were treated with abdominal hair removal, followed by covering with black polyethylene film transdermal patch of evodiae extract. The concentrations of evodiamine and rutacarpine in the subcutaneous tissues at different time points were measured by microdialysis sampling technique combined with HPLC method. RESULTS The maximum concentration(ρ_max) of evodiamine in the dialysate was(417.24±43.44) μg·mL^-1, time to peak concentration(t_max) was(4.210 ± 0.630) h, and the area under the concentration time curve(AUC_0→20) was (3 189.31 ± 789.97) μg·h·mL^-1; the ρ_max of rutacarpine was(287.13 ± 26.78) μg·mL^-1, t_max was(3.980 ± 0.580) h, and the AUC_0→16 was(1 327.97 ± 245.87) μg·h·mL^-1. CONCLUSION In vivo microdialysis sampling technique combined with HPLC method can be used for the evaluation of transdermal drug release characteristics of evodiamine and rutacarpine. The method has the advantages of simple operation with high sensitivity and specificity. Evodiamine and rutacarpine in evodiae extract have the characteristics of slow transdermal penetration speed but high penetration amount.