【摘要】 目的建立测定大鼠血浆中槲皮素、山柰素浓度的反相高效液相色谱法,研究银杏酮酯颗粒及其HP-β-环糊精包合物大鼠灌胃后体内药物动力学行为。方法血浆标本水解后,经乙酸乙酯提取,以甲醇-水-磷酸为流动相;12只大鼠随机均分为2组,分别灌胃银杏铜酯颗粒及其包合物后,检测血浆药物浓度。药时曲线采用DAS药代计算程序处理。结果槲皮素在2.6~264.0μg.mL-1,山柰素在1.2~120μg.mL-1与峰面积线性关系良好。结果表明GBE50经包合后,槲皮素主要药动学参数Cmax,tmax,AUC0-t,AUC0-∞分别为(0.219 4±0.034 5)mg.L-1、(4±1)h、(0.872±0.243)h.mg.L-1、(0.843±0.431)h.mg.L-1;参比制剂中槲皮素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为(0.164 6±0.004 1)mg.L-1、(8±3)h、(0.434±0.132)h.mg.L-1、(0.577±0.143)h.mg.L-1。GBE50经包合后山柰素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为(0.016 3±0.003)mg.L-1、(1±0.2)h、(0.077±0.023)h.mg.L-1、(0.09±0.04)h.mg.L-1;参比制剂中山柰素主要药动学参数Cmax、tmax、AUC0-t、AUC0-∞分别为(0.015 5±0.002)mg.L-1、(8±3)h、(0.023±0.003 5)h.mg.L-1、(0.026±0.011 2)h.mg.L-1.以槲皮素计,包合物的相对生物利用度为146.10%;以山柰素计,包合物的相对生物利用度为346.15%。结论该法准确,适用于槲皮素和山柰素血浆浓度的测定;制备的银杏酮酯-羟丙基-β-环糊精包合物与银杏铜酯颗粒相比,吸收明显增加。更多还原

【Abstract】 Objective To establish an RP-HPLC method for the determination of quercetin and kaempferol concentration and study the pharmacokinetic behaviors of quercetin and kaempferol in rats after administration of GBE50 and its complex(GBE50-HP-β-CD).Methods Drug in the plasma was extracted and determined by HPLC.The mobile phase was composed of methanol-water-orthophosphoric acid.Twelve rats randomized into 2 groups were given GBE50 and its complex respectively.The pharmacokinetic parameters were calculated by DAS software.Results The concentration-time data of GBE50 after the oral administration best fit the one-compartment model.The main pharmacokinetic parameters of quercetin were as follows: the Cmax,tmax,AUC0-t,AUC0-∞ of the test sample was(0.219 4±0.034 5)mg·L-1-1,(4±1)h,(0.872±0.243)h·mg·L-1,and(0.843±0.431) h·mg·L-1;that of the reference was(0.164 6±0.004 1)mg·L-1,(8±3)h,(0.434±0.132) h·mg·L-1,and(0.577±0.143)h·mg·L-1.The main pharmacokinetic parameters of kaempferol were as follows: the Cmax,tmax,AUC0-t,AUC0-∞ of the test sample was(0.016 3±0.003)mg·L-1,(1±0.2)h,(0.077±0.023)h·mg·L-1,(0.09±0.04) h·mg·L-1;that of the reference was(0.015 5±0.002)mg·L-1,(8±3)h,(0.023±0.003 5) h·mg·L-1,and(0.026±0.011 2)h·mg·L-1.Conclusion The method is suitable for the determination of quercetin and kaempferol plasma concentration in rats.Absorption in GBE50-HP-β-CD complex has increased compared with that of GBE50.更多还原