苦龙胆酯苷在大鼠体内的药代动力学研究

Study on the pharmacokinetics of amarogentin in rats

目的建立测定大鼠血浆中苦龙胆酯苷质量浓度的HPLC方法,研究苦龙胆酯苷在大鼠体内的药代动力学过程。方法雄性SD大鼠,尾静脉注射苦龙胆酯苷6.25,12.5和25mg·kg^-1,于不同时间采集血液。色谱柱为Woburn Stamsil C18,流动相为甲醇-水（40∶60）,流速为1.0mL·min^-1,柱温为30℃,内标为胡黄连苷Ⅰ,检测波长为260nm,应用药代动力学软件DAS 2.0拟合房室模型,并进行药代动力学参数的计算和数据分析。结果在选定的条件下,苦龙胆酯苷和胡黄连苷Ⅰ峰形良好,二者峰面积比值与苦龙胆酯苷血药质量浓度在一定范围内线性关系良好（r=0.999 4）,线性范围在0.114-114μg·mL^-1,日内和日间精密度RSD均小于10%,提取回收率为101.1%-106.2%,稳定性的RSD均小于3%。大鼠尾静脉给药后,体内药代动力学过程符合二室模型,在6.25-25mg·kg^-1范围内,药物的最大血药质量浓度（Cmax）或进入体循环的药量（用AUC表示）的变化与给药剂量的改变不成正比。结论所建立的HPLC法简便、快捷、灵敏、准确,适用于苦龙胆酯苷的药代动力学研究。

Objective To establish a method for the determination of amarogentin in rat plasma ,and to study the pharmacokinetics of amarogentin in rats .Methods Male SD rats were injected amarogentin in three doses of 6 .25 ,12 .5 and 25 mg · kg^ -1 through cauda vein ,followed by collecting blood samples at different time .The separation was performed on the column of Woburn Stam‐sil C18 using methanol‐water （40∶60） as the mobile phase at a flow of 1 .0 mL · min^-1 .The column temperature and ultraviolet detection were set at 30 ℃ and 260 nm ,respectively .Picroside Ⅰ was chosen as an internal standard .The data were calculated by DAS2 .0 software .Results The determination method of amarogentin was established by HPLC .A good linear relationship was obtained between the peak‐area ratios of amarogentin and picroside Ⅰ and amarogentin′s concentration in plasma samples over the range of 0 .114‐114 μg · mL^ -1 （r=0 .999 4） .The RSD of inter‐day and intra‐day were both within 10% and the extraction re‐covery was between 101 .1% and 106 .2% .The RSDs of stability for plasma amarogentin were within 3% .The concentration‐time curve of amarogentin in rats plasma after iv administration fitted with the two‐compartment model .Within the range of 6 .25‐25 mg · kg ^-1 ,the Cmax and AUC did not show direct proportion with the dosage .Conclusion The method of detecting plasma am‐arogentin is simple ,rapid ,sensitive and accurate which is suitable for the pharmacokinetic study of plasma amarogentin in rats .