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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 establish a HPLC method for the determination of 5,7,3’-triacetyl-hesperetin (TAHP) in rat plasma and to investigate its pharmacokinetics in rats. Methods A C18 reversed-phase column was used with a linear gradient of methanol-0.5% glacial acetic acid as mobile phase. The flow rate was 1.0 ml / min. The detection wavelength was 288 nm and the column temperature was 40 ℃. Rats were given 25, 50, 100 mg / kg TAHP by single intragastric administration, and plasma samples were hydrolyzed by β-glucuronidase and determined by high performance liquid chromatography. Plasma concentration-time data was processed using DAS 2.0 software. Results Hesperidin showed good linearity (r = 0.999 7) in the range of 0.05-25 μg / ml. The recovery rates of all the samples were all above 80%. The intra-day and inter-day RSDs were less than 10%. The main pharmacokinetic parameters of hesperetin, a metabolite of TAHP (25,50,100 mg / kg), were Tmax (h): 1.30 ± 1.13,1.80 ± 1.30,3.17 ± 0.41; Cmax (mg / L) , 1.65 ± 0.34, 4.27 ± 0.84; AUC (0-t) (mg / hL): 7.57 ± 1.51, 17.84 ± 1.81, 61.67 ± 19.04. Conclusion The method is convenient, rapid, specific, accurate and reliable, and is suitable for the study of pharmacokinetics of TAHP in rats. The plasma concentration-time data of the metabolite hesperetin in a single dose of oral TAHP 3 dose group fit a two-compartment model that conforms to primary absorption.