微透析联合高效液相色谱法研究延胡索乙素在清醒大鼠脑局部的药动学

目的：研究延胡索乙素（THP）灌胃给药在清醒大鼠脑局部的药动学特性。方法：采用微透析采样技术，以清醒大鼠为实验模型，连续收集给药（40 mg·kg^-1）后大鼠脑纹状体透析液，高效液相色谱（HPLC）法测定THP浓度，经回收率校正后，用PK Solver 2.0药动学软件按非房室模型计算主要药动学参数。结果： THP在清醒大鼠脑局部的药动学参数t_1/2为（2.0±0.46） h；t_max为（1.18±0.19） h；C_max为（4 090.73±151.45） ng·mL^-1；AUC_0-inf为（15.05±1.02） ng·mL^-1·h^-1；MRT_0-inf为（3.72±0.21） h。结论：所采用的微透析技术能实现活体连续取样，所建立的HPLC分析方法经方法学考察表明该方法精密度、准确度高，重现性好；微透析-HPLC法适用于延胡索乙素在大鼠脑局部的药动学研究，为其脑部靶向制剂的开发与临床应用提供实验依据。

Brain pharmacokinetics of tetrahydropalmatine in free-moving rats investigated by microdialysis combined with HPLC

OBJECTIVE To study the pharmacokinetics of THP in rat brain after intragastric administration.METHODS Striatum dialysate samples were continuously collected by brain microdialysis technique in free moving rats after intragastric administration. The concentrations of THP in dialysate samples were measured by HPLC. The pharmacokinetic parameters were calculated by pharmacokinetic software PK Solver 2.0.RESULTS The t_1/2 was (2.0±0.46) h, t_max was (1.18±0.19) h, C_max was (4 090.73±151.45) ng·mL^-1, AUC_0-inf was (15.05±1.02) ng·mL^-1·h^-1, MRT_0-inf was (3.72±0.21) h.CONCLUSION The in vivo microdialysis method can achieve continuous sampling in rat brain. The precisions, accuracy and stability of the HPLC meet the requirements. Microdialysis-HPLC is suitable for pharmacokinetics of THP in rat brain and provides experimental basis for the development and clinical application of the THP brain targeting preparation.