基于液质联用技术的肺痹汤有效成分测定及药代动力学特征初探  

Discussion on effective components’determination of Feibi decoction and pharmacokinetics charicteristics based on LC-MS technology

作　　者：郝庆勋 李国栋 韦婉 谢洁 焦扬[2] HAO Qingxun;LI Guodong;WEI Wan;XIE Jie;JIAO Yang(Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学,100029 [2]北京中医药大学东方医院呼吸科

出　　处：《环球中医药》2020年第4期561-567,共7页Global Traditional Chinese Medicine

基　　金：北京市中医药薪火传承项目-周平安名医传承工作站。

摘　　要：目的通过液质联用技术研究肺痹汤有效成分及肺痹汤在大鼠体内的药代动力学改变。方法采用UPLC/Q-Tof仪对肺痹汤水煎剂药效物质基础进行检测;19只SD大鼠分为单次给药组、给药7天组及空白对照组,给药组大鼠按照单次及连续7天方法分别灌胃肺痹汤,空白对照组予7天等量生理盐水,灌胃后由股动脉插管进行不同时间段采血,质控样品复溶后采用Waters XEVOTQ-S质谱仪在负离子模式下测定大鼠含药血浆中三种成分的血药浓度并计算药代动力学参数。结果肺痹汤在浓度为1~1600 ng/mL范围内线性关系良好,定量下限为1 ng/mL。低中高浓度分别为20、200和1200 ng/L的血浆质控样品,其方法学给药7天组考察中相对标准偏差均小于15%。肺痹汤给药后药代动力学参数曲线符合房室模型,通过比较单次给药组与给药7天组各成分的药代动力学参数,7天给药组中MRT、t1/2明显增加,CLz/F降低,AUC0-t、Cmax增高,在20~1200 ng/L范围内线性关系良好。结论本实验方法可测定肺痹汤水煎剂及大鼠含药血浆相关有效物质的含量,并发现肺痹汤7天给药较单次给药可提高药物成分在大鼠体内的暴露水平。Objective To study the effective components of Feibi decoction and its pharmacokinetic changes in rats by using the liquid chromatography-mass spectromety(LC-MS)technology.Methods The pharmacodynamic basis of Feibi decoction was detected by UPLC/Q-TOF instrument.19 SD rats were divided into single dose group,7-day dose group and blank group.The rats in single dose group were given a gavage of Feibi decoction once time,the rats in 7-day dose group were given a gavage of Feibi decoction for 7 consecutive days,and the rats in the blank group were given a gavage of the same amount of normal saline for 7 consecutive days.After gavage,blood was collected at different time by intubation of femoral artery.After the quality control samples were redissolved,the plasma concentrations of the three components in rat plasma were determined by Waters XEVOTQ-S mass spectrometer in anion mode and the pharmacokinetic parameters were calculated.Results The linear relationship was good in the range of the F eibi decoction at the concentration of 1~1600 ng/mL,and the lower limit of quantitation was 1ng/mL.For the plasma quality control samples with low,medium,and high concentrations of 20,200 and 1200 ng/L,the relative standard deviation was less than 15%in the 7-day group.The pharmacokinetic parameter curves of Feibi decoction were consistent with the atrioventricular model.The pharmacokinetic parameters of each component in the single dose group and the 7-day dose group were compared,MRT and t 1/2 significantly increased,CLz/F decreased,AUC 0-t and Cmax in the one-week dose group were higher than those in the single dose group,and the linear relationship was good between the concentration of 20~1200 ng/L.Conclusion This experiment method can be used to determine the effective substances of Feibi decoction related to medicated plasma in rats.And it was found that the 7-day administration of Feibi decoction could improve the exposure level of drug components in rats compared with single administration.

关 键 词：液质联用技术 肺痹汤 含药血浆 血药浓度 有效成分测定 药代动力学 

分 类 号：R285[医药卫生—中药学]