大鼠股静脉给药五味子酚的药动学研究

目的建立测定大鼠血浆中五味子酚浓度的HPLC方法,并对五味子酚在大鼠体内的药动学特征进行研究。方法血浆样品经甲醇沉淀及乙醚萃取后,用HPLC-DAD进行测定分析。色谱柱为Eclipse XDB-C18Agilent(250 mm×4.6 mm,5μm),流动相为乙腈-水(65∶35),检测波长254 nm;测定大鼠静脉注射五味子酚18 mg/kg后的血药浓度,并利用3P87软件拟合其药动学参数。结果五味子酚的血药浓度在0.1~2.5μg/mL线性关系良好(r2=0.999),最低检测限为10 ng/mL,在3个浓度水平下,方法的回收率为88%~110%,日间和日内RSD小于15%,符合生物样品分析要求。大鼠股静脉注射18 mg/kg后,血药浓度-时间曲线呈二室模型。主要药动学参数t1/2α、t1/2β、V、AUC、MRT分别为(0.22±0.11)h、(1.19±0.22)h、(12.81±2.91)L/kg、(1.32±0.19)μg/mL/h、(1.51±0.24)h。结论该方法简便、快速、稳定可靠,适用于五味子酚的体内分析。

Pharmacokinetic study of sclusanhenol via femoral intravenous administration in rats

Objective To establish an HPLC method for the determination of schisanhenol in plasma and to study the pharmacokinetics of schisanhenol in rats. Methods After sedimentation by methanol, plasma samples were then prepared based on a liquid-liquid extraction by ether. The extracted samples were analyzed by liquid chromatography. Schisanhenol was eluted on Eclipse XDB-C_(18) Agilent (250 mm× 4.6 mm, 5 μm) column, using a mobile phase of acetonitrile-H_2O (65 : 35), and detected at 254 nm. The plasma concentration of schisanhenol in rats was determined after iv administration of 18 mg/kg, and the data were processed with the pharmacokinetic software 3P87. Results Calibration curves were linear over 0.1-2.5 μg/mL (r~2 =0.999) and the LOD was 10 ng/mL. The recoveries of schisanhenol from plasma were between 88%-110%, and the RSD values of intra-day and inter-day assay were below 15%. After iv administration at 18 mg/kg, the schisanhenol concentration-time curve confirmed in a two-compartment model and the pharmacokinetic parameters of t_(1/2α), t_(1/2β), V, AUC, MRT were (0.22±0.11) h, (1.19± 0.22) h, (12.81±2.91) L/kg, (1.32±0.19) μg/mL/h, (1.51±0.24) h, respectively. Conclusion A reliable HPLC-DAD method is developed for the determination of schisanhenol in rat plasma and it is appli-cable to the in vivo analysis.