液相色谱-串联质谱法测定人血浆中染料木素及其葡萄糖醛酸代谢物  

Determination concentration of genistein and glucuronidated genistein in human plasma by LC/MS/MS

作　　者：冯怡[1] 曾星[1] 邓远辉[1] 唐波[1] 孙丽[1] 刘奕明[1] 杨柳[1] 

机构地区：[1]广州中医药大学第二临床医学院中心实验室,广州510120

出　　处：《中国临床药理学杂志》2010年第1期64-67,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技支撑计划课题基金资助项目(2006BAI14B00);广东省中医药局建设中医药强省科研课题资助项目(2008321)

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50mg，血浆加入内标物地塞米松后，经液-液萃取，色谱柱为Capcell Pak C8（2mm×150mm，5μm），流动相为：甲醇-5mmol·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DAS2．0程序计算药代动力学参数。结果线性范围为0．3～500．0μg·L^-1（1=0．9983），回收率在92．9％～104．9％，绝对回收率在74．2％～89．2％，13内、13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±I．3），（6．0±2．4）h，Cmax分别为（10．1±6．3），（218．7±68．6）μg·L^-1，AUC0-1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。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： t 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, AUC0-1 were （31.2 ± 10. 3） and （3344.0 ± 1635.0） μg·L^-1, AUC0-1 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

关 键 词：液相色谱-串联质谱 染料木素 葡萄糖醛酸化代谢物 血药浓度 药代 动力学 

分 类 号：R977.12[医药卫生—药品] R969.1[医药卫生—药学]