摘要
目的:基于UPLC-MS/MS技术,研究大鼠灌胃千金子生品、霜品提取物后千金子素L_(1)、千金子素L_(2)和千金子素L_(3)的尿液及粪便的排泄动力学特征。方法:SD大鼠灌胃给予千金子生品、霜品提取物,收集不同时间段的尿液和粪便,采用建立的UPLC-MS/MS方法对千金子制霜前后3个二萜醇酯类成分的浓度进行测定,以DAS 2.0软件计算尿排泄动力学参数,绘制累积排泄率及排泄速率曲线,比较制霜前后的排泄动力学差异。结果:灌胃给药千金子提取物96 h后,千金子素L_(1)、L_(2)和L_(3)在尿液中的累积排泄率分别为0.009%、0.008%、0.009%,在粪便中的累积排泄率分别为16.05%、51.57%、36.33%;灌胃给药千金子霜提取物96 h后,千金子素L_(1)、L_(2)和L_(3)在尿液中的累积排泄率分别为0.014%、0.01%、0.011%,在粪便中的累积排泄率分别为27.32%、59.03%、35.97%。结论:千金子3个二萜醇酯类成分在体内主要通过粪便排泄,制霜后在尿液的半衰期t_(1/2)减小,消除速率常数k_(e)增大,其制霜后毒性减弱可能与药物从体内的排泄量增加、在体内蓄积减少有关。
Objective:The characteristics of excretion kinetics of euphorbia factor L_(1),L_(2) and L_(3) in rat urine and feces were studied after intragastric administration of crude and frost extracts of Euphorbiae Semen based on UPLC-MS/MS technology.Methods:The SD rats were respectively gavaged with crude and frost extracts of Euphorbiae Semen,then urine and feces of the rats were collected before and after administration.The concentrations of three diterpene esters of Euphorbiae Semen before and after frosting were determined by the established UPLC-MS/MS method.The urinary excretion kinetic parameters were calculated by DAS 2.0 software,the cumulative excretion rate and excretion rate curves were drawn,and the differences of excretion kinetics before and after frosting were compared.Results:After 96 hours of oral administration of Euphorbiae Semen extract,the cumulative excretion rates of euphorbia factor L_(1),L_(2) and L_(3) in urine were 0.009%,0.008% and 0.009%,respectively,and the cumulative excretion rates in feces were 16.05%,51.57%and 36.33%,respectively.After 96 hours of oral administration of Euphorbiae Semen pulveratum extract,the cumulative excretion rates of euphorbia factor L_(1),L_(2) and L_(3) in urine were 0.014%,0.01% and 0.011%,respectively,and the cumulative excretion rates in feces were 27.32%,59.03% and 35.97%,respectively.Conclusion:The three diterpenoid alcohol esters of Euphorbiae Semen were mainly excreted through feces.After frosting,the t_(1/2) of euphorbia factor L_(1),L_(2) and L_(3) decreased,while the k_(e) increased.The decrease of toxicity Euphorbiae Semen after frosting may be related to the increase of drug excretion from the body and the decrease of drug accumulation in vivo.
作者
王佩华
王英姿
王慧楠
杨子烨
张桂梅
陈梦雨
姜明瑞
岳珠珠
王志成
张婧秋
WANG Pei-hua;WANG Ying-zi;WANG Hui-nan;YANG Zi-ye;ZHANG Gui-mei;CHEN Meng-yu;JIANG Ming-rui;YUE Zhu-zhu;WANG Zhi-cheng;ZHANG Jing-qiu(College of Chinese Meteria Medica,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2021年第11期1904-1913,共10页
Chinese Journal of Pharmaceutical Analysis
基金
国家自然科学基金项目(82074021)。
