摘要
目的建立大鼠血浆中肉桂酸(cinnamic acid,CA)、香草酸(vanillic acid,VA)和3,3'-O-二甲基鞣花酸(3,3'-O-dimethylellagic acid,DMA)浓度测定的液相色谱-串联质谱联用(LC-MS/MS)分析方法,研究给药不同剂量安神补心六味丸(Anshen Buxin Liuwei Pills,ASBX)后3种成分的药动学过程及量暴关系。方法雄性SD大鼠灌胃给药不同剂量ASBX后采集不同时间点血浆并采用蛋白沉淀法处理,采用LC-MS/MS法测定血浆中CA、VA和DMA的浓度,用MaS Studio软件计算药动学参数,采用置信区间法分析给药剂量和系统暴露水平的相关性。结果在线性范围内3种化合物线性关系良好,该方法专属性、精密度与准确度、回收率、基质效应和稳定性均满足生物样品的测定要求。大鼠单次灌胃给药ASBX后,CA、VA和DMA的tmax分别为0.22~0.40、0.08和5.40~8.20 h,t_(1/2)分别为在0.79~2.04、0.37~0.65和4.26~9.58 h,ρmax分别为279.70~302.88、16.42~43.33、2.81~7.20 ng·mL^(-1),AUC_(0-∞)分别为351.83~537.96、7.20~18.82、29.27~119.64 ng·h·mL^(-1)。随着给药剂量的增加,VA和DMA在大鼠体内的ρmax和AUC,以及CA的AUC均与剂量呈正相关,但是CA的ρmax则与剂量无明确相关性。结论该分析方法快速、灵敏、准确,适合大鼠灌胃给药ASBX后的药动学研究,为其药效物质基础研究和临床安全有效用药提供了参考。
OBJECTIVE To establish a liquid chromatography tandem mass spectrometry(LC-MS/MS)method for determination of cinnamic acid(CA),vanillic acid(VA)and 3,3'-O-dimethylellagic acid(DMA)concentrations in rat plasma and evaluate the pharmacokinetics and the correlations between dose and systemic exposure levels of CA,VA and DMA in rats after single dose administration of Anshen Buxin Liuwei Pills(ASBX).METHODS Blood was collected from male SD rats at different time points after different dose administration.The plasma was processed by protein precipitation method.The concentrations of CA,VA and DMA in plasma were determined by LC-MS/MS method.Pharmacokinetic parameters were calculated with MaS Studio software.The correlations between dose and systemic exposure level were analyzed by confidence interval method.RESULTS The linear relationship of the calibration curves of the three compounds were good within the tested ranges,and the specificity,precision and accuracy,recovery,matrix effect and stability of the method all met the requirements for biological sample assay.After single intragastric administration of ASBX,the tmax of CA,VA and DMA were 0.22-0.40,0.08 and 5.40-8.20 h,the t_(1/2) were 0.79-2.04,0.37-0.65 and 4.26-9.58 h,theρmax were 279.70-302.88,16.42-43.33,and 2.81-7.20 ng·mL^(-1),and the AUC_(0-∞)were 351.83-537.96,7.20-18.82,and 29.27-119.64 ng·h·mL^(-1),respectively.The results of confidence interval analysis showed that theρmax and AUC of VA and DMA,and AUC of CA were positively correlated with dose,but theρmax of CA was not clearly correlated with dose.CONCLUSION The LC-MS/MS analysis method is proved to be rapid,sensitive,and accurate,so it can be applied to the pharmacokinetic study of ASBX after intragastric administration in rats.This sdtudy provides a reference for future research on the pharmacodynamic material basis and safe and effective clinical use of ASBX.
作者
王翼遥
黄鹤
高云航
宋玲
李晗
王慧颖
彭博
侯红平
叶祖光
陈俊苗
张广平
陈腾飞
WANG Yiyao;HUANG He;GAO Yunhang;SONG Ling;LI Han;WANG Huiying;PENG Bo;HOU Hongping;YE Zuguang;CHEN Junmiao;ZHANG Guangping;CHEN Tengfei(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Liaoning Normal University,Dalian 116000,China;Beijing Application Center,SCIEX China,Beijing 100010,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2024年第17期1620-1628,共9页
Chinese Pharmaceutical Journal
基金
国家重点研发计划项目资助(2018YFC1708200,2018YFC1708204)
内蒙古自治区科技重大专项资助(2019ZD004)。
