5,7,3＇-三乙酰橙皮素在大鼠体内的药代动力学研究

Pharmacokinetics of 5,7,3′-triacetyl hesperetin in rats

目的建立高效液相色谱法测定5,7,3'-三乙酰橙皮素(TAHP)在大鼠血浆中的浓度,并探讨其在大鼠体内的药代动力学。方法采用C18反相色谱柱,以甲醇-0.5%冰醋酸为流动相线性梯度洗脱,流速1.0 ml/min,检测波长288nm,柱温40℃。单剂量灌胃给予大鼠25、50、100 mg/kg的TAHP,血浆样品经β-葡萄糖醛酸酶水解后用高效液相色谱法测定。血药浓度-时间数据用DAS 2.0软件处理。结果橙皮素在0.05～25μg/ml范围内线性关系良好(r=0.999 7),各样品的提取回收率均大于80%,日内、日间精密度RSD均小于10%。TAHP(25、50、100 mg/kg)的代谢物橙皮素的主要药动学参数Tmax(h):1.30±1.13、1.80±1.30、3.17±0.41;Cmax(mg/L):0.90±0.13、1.65±0.34、4.27±0.84;AUC(0-t)(mg/h.L):7.57±1.51、17.84±1.81、61.67±19.04。结论该方法方便快捷,专属性强,准确可靠,适用于TAHP在大鼠体内的药代动力学研究。单剂口服TAHP3个剂量组的代谢物橙皮素的血药浓度-时间数据拟合符合一级吸收的二室模型。

Objective To develop an HPLC detection for the quantification of 5,7,3′-triacetyl hesperetin（TAHP） in rat plasma and study the pharmacokinetics in rats.Methods A C18 reversed-pase chromatography column was used,and the mobile phase of methyl alcohol-0.5% glacial acetic acid was applied to perform gradient dilution at flow rate of 1.0 ml/min.The detection wavelength was set at 288 nm and the column temperature was 40℃.A single oral dose of TAHP was performed in SD rats at 25,50,100 mg/kg.Plasma sample was prepared after hydrolysis with β-glucuronidase and determined by HPLC.Plasma concentration-time data were analyzed by DAS 2.0.Results The calibration curve was linear within 0.05~25 μg/ml（r=0.999 7）.The recoveries were more than 80%,with the intraday-and interday-RSDs less than 10%.The main pharmacokinetic parameters（25,50,100 mg/kg） were Tmax（h）： 1.30±1.13,1.80±1.30,3.17±0.41;Cmax（mg/L）： 0.90±0.13,1.65± 0.34,4.27±0.84;AUC（0-t）（mg/h·L）： 7.57±1.51,17.84±1.81,61.67±19.04,respectively.Conclusion The method is proved to be convenient,rapid,accurate and specific and has been successfully applied to pharmacokinetic study in rats.The plasma drug concentration-time data curve of the active metabolite of TAHP conforms to two compartments model of the first level absorption.