基于血液微透析技术探究五味子甲素的体内代谢过程

Exploration of Deoxyschizandrin Metabolic Processes in Vivo Based on Blood Microdialysis

目的 建立高效液相色谱法测定大鼠血浆中五味子甲素的方法,探讨五味子甲素在大鼠血中的代谢过程.方法 采用血液微透析技术,将探针由右侧颈静脉植入大鼠右心房膨大处,透析取样.透析液检测的色谱条件为：以甲醇-乙腈-水（40∶35∶25）为流动相,流速1.0 mL/min,柱温30 ℃,UV 检测波长254 nm.经体内测定探针的回收率校正后,绘制药时曲线,采用DAS2.0 软件计算五味子甲素灌胃给药后在大鼠血液中的药动学参数.结果 五味子甲素在2～500 μg/mL 浓度范围内线性关系良好（r=0.999 5）,日内精密度和日间精密度均RSD〈3%,五味子甲素的含药透析液室温放置12 h 内稳定性良好.药动学参数ke 为（0.364±0.047）/h,t1/2 为（1.637±0.302）h,Tmax 为（0.612±0.194）h,Cmax 为（165.92±28.830）μg/mL,AUC0-t 为（240.793±25.540）μg·h/mL,AUC0-∞为（282.710±30.727）μg？h/mL.结论 本方法操作便捷、液相保留时间短,能满足透析液中五味子甲素含量测定的需要,可用于五味子甲素在大鼠血液中代谢过程的研究.

Objective To establish an HPLC method for evaluating deoxyschizandrin in rat plasma; To exploredeoxyschizandrin metabolic processes in blood. Methods The blood microdialysis probe was implanted into the rightatrial enlargement through right jugular vein to detect the concentration of deoxyschizandrin in blood.Chromatographic conditions for detecting of dialysis fluid were as follows： mobile phase was methanol-acetonitrilewater（40：35：25）; flow rate was 1 mL/min; column temperature was 30 ℃; UV detection wavelength was 254 nm.The data obtained after being calculated by the recovery rate of the probe in vivo were dealt with DAS 2.0 software.Pharmacokinetic parameters were calculated, and the concentration-time related curves were plotted. Results Thedeoxyschizandrin curve was linear （r=0.999 5） within the range of 2–500 μg/mL. The RSD of intra-day pecision andinter-day pecision were both 〈3%. The stability of the solution was good in 12 hours at roomtemperature. ke was（0.364±0.047）/h; t1/2 was （1.637±0.302）h; Tmax was （0.612±0.194）h; Cmax was （165.92±28.830） μg/mL; AUC0-t was（240.793±25.540） μg？h/mL; AUC0-∞ was （282.710±30.727） μg？h/mL. Conclusion The method is convenient toperform, and the retention time of HPLC is short. This method is suitable for detecting the content ofdeoxyschizandrin in dialysis fluid, which can also be used to investigate the metabolic processes of deoxyschizandrinin the rat blood.