白果中止咳化合物GK-A在大鼠尿液和胆汁中的排泄行为分析  

Analysis of Excretion Behavior of GK-A from Ginkgo Semen in Urine and Bile of Rats

作　　者：张庆[1] 王晴 程锦堂[1] 刘安[1] 王跃生[1] ZHANG Qing;WANG Qing;CHENG Jin-tang;LIU An;WANG Yue-sheng(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]北京中医药大学东直门医院,北京100700

出　　处：《中国实验方剂学杂志》2020年第3期96-101,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：中国中医科学院自主选题项目(L2017047)。

摘　　要：目的:研究白果中有止咳作用的新化合物GK-A在大鼠尿液和胆汁中的排泄行为。方法:利用UPLC-MS/MS测定大鼠尿液和胆汁中GK-A的含量,色谱分离采用C18色谱柱,流动相0.1%甲酸水溶液(A)-乙腈(B)梯度洗脱(0~1 min,95%A;1~3 min,95%~85%A;3~7.5 min,85%~40%A;7.5~8 min,40%A),流速0.2 mL·min-1,柱温35℃,进样量0.5μL;质谱采用电喷雾离子源,在正离子模式下采用多重反应监测(MRM)方式测定,GK-A和GK-2(内标)的定量离子对分别为m/z 453.1~291.1,467.0~305.1。大鼠灌胃给予GK-A后,收集不同时间段尿液和胆汁,测定样品中GK-A的含量,计算其累积排泄量和累积排泄率。结果:给药72 h后GK-A在大鼠尿液中的累积排泄量(12.35±2.69)μg,累积排泄率(0.58±0.13)%;给药24 h后GK-A在大鼠胆汁中的累积排泄量(55.16±29.22)μg,累积排泄率(1.57±0.83)%。GK-A原型经大鼠尿液和胆汁排泄的量较少,且排泄速度慢。结论:灌胃给药后,GK-A原型经大鼠尿液和胆汁的排泄不是其主要的消除途径。Objective:To investigate excretion of GK-A,a antitussive compound separated from Ginkgo Semen,in the urine and bile of rats.Method:UPLC-MS/MS was used to determine the concentration of GK-A in rat urine and bile samples.The separation was performed on a C18 column,the mobile phase consisted of 0.1%formic acid aqueous solution(A)and acetonitrile(B)for gradient elution(0-1 min,95%A;1-3 min,95%-85%A;3-7.5 min,85%-40%A;7.5-8 min,40%A).The detection was carried out by a triple quadrupole mass spectrometer in the positive ion mode with an electrospray ionization(ESI).Multiple reaction monitoring(MRM)mode was employed.After intragastric administration of GK-A,the urine and bile samples were collected at different time points,and the contents of GK-A in the samples were determined,and the cumulative excretion and cumulative excretion rate were calculated.Result:After 72 h of administration,the cumulative excretion of GK-A in urine was(12.35±2.69)μg,and the cumulative excretion rate was(0.58±0.13)%.Meanwhile,after 24 h of administration,the cumulative excretion of GK-A in bile was(55.16±29.22)μg,and the cumulative excretion rate was(1.57±0.83)%.Only a small amount of GK-A was excreted from urine and bile of rats with a slow speed.Conclusion:After intragastric administration,the excretion of GK-A in rat urine and bile is not the main elimination pathway.

关 键 词：白果 GK-A 尿液 胆汁 排泄行为 止咳作用 新药开发 

分 类 号：R22[医药卫生—中医基础理论] R969.1[医药卫生—中医学]