天麻素药代动力学和组织分布特征研究

目的: 建立HPLC-UV测定大鼠血浆和组织中天麻素的方法,研究不同给药方式下天麻素在大鼠体内药代动力学和组 织分布特征。方法: 采用沉淀蛋白法预处理血浆和组织样品,采用岛津Shim-pack VP-ODS柱分离,以甲醇-水(15:85)为流动相,流速1.0 mL·min^-1,检测波长195 nm,柱温40℃。结果: 天麻素大鼠血浆质量浓度在0.1~100 μg·mL^-1范围,组织质量浓度在0.2~200 μg·mL^-1范围色谱响应线性关系良好。大鼠灌服天麻素符合一房室模型,t_max=0.38 h,C_max=10.78 μg·mL^-1,t_1/2=1.43 h,AUC_0-∞=9.45 μg·h·mL^-1。静脉注射符合二房室模型,t_1/2=1.30 h,AUC_0-∞=28.06 μg·h·mL^-1,绝对生物利用度为(33.94±3.67)%;天麻素可以透过血脑屏障,但在脑组织中浓度较低。结论: 建立了大鼠血浆及组织中天麻素的HPLC-UV测定方法并进行了方法学验证,此方法简便、快速,结果准确、可靠;首次阐明了不同给药方式下天麻素在大鼠体内药代动力学和组织分布特征。

Objective: To establish an HPLC-UV method to determine gastrodin in plasma and tissues of rats, and to study its pharmacokinetic behaviour and tissue distribution characteristics. Methods: The biotic samples were prepared by one-step protein precipitation followed by an isocratic elution with methanol-water(15: 85)on a Shim-pack VP-ODS C₁₈ column.The flow rate was 1.0 mL·min^-1, the detection wavelength was 195 nm, and the column temperature was 40℃. Results: Good linearity was obtained in plasma with in the range of 0.1-100 μg·mL^-1 range and every kind of tissue over 0.2-200 μg·mL^-1 .Intragastric administration to rats, the pharmacokinetic characteristics of gastrodin complied with the mono-compartment model:t_max=0.38 h, C_max=10.78 μg·mL^-1, t_1/2=1.43 h, AUC_0-∞=9.45 μg·h·mL^-1.After ig administration to rats, the pharmacokinetic characteristics of gastrodin complied with the two-compartment model:t_1/2=1.30 h, AUC_0-∞=28.06 μg·h·mL^-1.The results indicated that gastrodin could permeate the blood-brain barrier and the absolute bioavailability was(33.94±3.67)%. Conclusion: The established method is sensitive, accurate and reproductive, which provides a reliable means for the qualitative and quantitative study of gastrodin in biotic samples.In addition, it is the first time to study the pharmacoinetic characters and tissue distribution of gastrodin in rats after different administrations.