摘要
目的 建立大鼠肝微粒体中葛根素及其代谢物的液相色谱一质谱测定法。并研究葛根素在大鼠肝微粒体中的药物代谢动力学。方法 色谱柱为Waters C18柱（150mm×4．6mm，5μm），流动相为甲醇-水（体积比为50：50），通过电喷雾电离源（ESI），以正离子方式进行检测。结果 方法的回收率为95．6％～96．8％。其日内、日间的RSD分别为4．9％～7．6％和3．7％～6．2％，葛根素的质量浓度在0．5～20mg·L^-1内与峰面积呈良好的线性关系。在温孵时间0-40min内、微粒体蛋白质量浓度在0．5～2．0g·L^-1内，葛根素呈线性消除，随着肝微粒体蛋白质量浓度的增大，葛根素呈线性消除。葛根素可被肝微粒体代谢成大豆苷元。其代谢机理为还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）依赖性的氧化代谢。还原型烟酰胺二核苷酸（NADH）对葛根素代谢基本没有催化作用。结论 葛根素在大鼠肝微粒体内被迅速代谢，大鼠肝微粒体P450酶参与了葛根素的代谢。
Objective To develop a LC-MS method for the determination of puerarin and its metabolite and study the kinetics of its metabolism in rat liver microsomes. Methods Chromatography was performed on a Waters C18 column（150mm×4.6mm,5μm）. A methanol-water（ V： V = 50 ： 50） as the mobile phase was used. A Waters Micromass ZQ detector equipped with an ESI interface was used and operated in the positive ion mode. Results The recovery of of puerarin for the proposed method was 95.6 % - 96.8 %. The relative standard deviation for the wlthin-day and between-day were 4.9% - 7.6% and 3.7% - 6.2%. The calibration curve was linear in the range from 0.5 mg·L^- 1 to 20 mg·L^- 1 with r = 0. 999 5. The elimination of puerarin was linear. Microsomal protein concentration had significant effect on puerarin metabolism. One metabolite of puerarin was found to be daidzein. The metabolism of puerarin exhibited NADPH-dependent oxidation mechanism. NADH as cofactor had no catalytic effect on the metabolism of puerarin. Conclusions Puerarin is rapidly metabolized in rat liver microsomes. The result suggests that CYP450 is involved in the metabolism of puerarin.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2007年第1期32-36,共5页
Journal of Shenyang Pharmaceutical University
作者简介
崔升淼（1974-），女（汉族），辽宁大连人，博士。主要从事药物新剂型的研究。Tel．020—39352169，E—mail cuishengmiao@yahoo．com；
何仲贵（1965-），男（汉族），宁夏盐池人，教授。博士生导师，主要从事药物新剂型和生物药剂学研究，Tel，024-23986321，E-mail cnhzg@tom．com。
