【摘要】 目的建立液相色谱-串联质谱联用法测定人血浆中染料木素(雌激素类药物)及其葡萄糖醛酸代谢物(GGS)并研究其在健康人体中的药代动力学。方法10例健康受试者空腹口服染料木素50 mg,血浆加入内标物地塞米松后,经液-液萃取,色谱柱为Capcell Pak C8(2 mm×150 mm,5μm),流动相为:甲醇-5 mmol.L-1乙酸铵-乙腈(70∶20∶10),以ESI源正离子MRM模式测定染料木素的血药浓度,GGS先酶解为原形后间接测定,用DAS 2.0程序计算药代动力学参数。结果线性范围为0.3~500.0μg.L-1(γ=0.9983),回收率在92.9%~104.9%,绝对回收率在74.2%~89.2%,日内、日间变异(RSD)均<15%。染料木素和GGS的主要药代动力学参数:tmax分别为(5.0±1.3),(6.0±2.4)h,Cmax分别为(10.1±6.3),(218.7±68.6)μg.L-1,AUC0-t分别为(31.2±10.3),(3344.0±1635.0)μg.h.L-1,AUC0-∞分别为(33.9±11.4),(3703.0±2031.0)μg.h.L-1。结论测定方法灵敏、准确、快速、特异性强,适用于染料木素药代动力学研究。更多还原

【Abstract】 Objective To establish a LC/MS/MS method in order to determine concentration of genistein and glucuronidated genistein(GGS) in plasma,and study its pharmacokinetics in healthy human.Methods Ten healthy volunteers were given a single oral dose of genistein 50 mg.The plasma sample were prepared by liquid-liquid extraction method with ethyl acetate,used the Capcell Pak C8(2 mm×150 mm,5 μm) as analytical column,the mobile phase consisted of methanol-5 mmol L-1 NH4AC buffer-acetonitrile(70∶20∶10).The plasma concentrations were detected in ESI positive MRM mode,and the GGS was hydrolyzed to genistein and detected indirectly.The pharmacokinetic parameters were analyzed by DAS(ver 2.0).Results The good linear range of genistein was 0.5-500.0 g·L-1(γ=0.9983).The recovery and the Absolute recovery was 92.9%-104.9% and 74.2%-89.2%,respectively.The within-day and between-day deviations were less than 15%.The pharmacokinetic parameter of genistein and GGS were as follows: tmax were(5.0± 1.3) and(6.0±2.4) h,Cmax were(10.1±6.3) and(218.7±68.6) μg·L-1,AUC0-t were(31.2± 10.3) and (3344.0±1635.0) μg·L-1·h,AUC0-∞were(33.9±11.4) and(3703.0±2031.0) μg·h·L-1.Conclusion The method was sensitive,accurate,rapid,specific,suitable for pharmacokinetics study of genistein.更多还原