摘要
目的比较五味子不同炮制品中3种木脂素在大鼠体内的含量差异,为五味子“入补药熟用”提供药动学依据。方法18只SD大鼠随机分为生五味子、酒五味子、醋五味子3组,每组6只。分别灌胃给予相应五味子水提液2 g·kg-1(为生药量),以牛蒡苷元为内标物,血浆样品经甲醇沉淀蛋白,采用UPLC-MS/MS正离子MRM模式下测定不同时间点大鼠血浆中五味子甲素、五味子乙素、五味子醇甲的浓度,并对不同时点的血药浓度数据采用DAS 3.2.7软件拟合,计算其药动学参数。结果大鼠血浆样品中,五味子甲素、五味子乙素、五味子醇甲的线性范围分别为0.180~12.625μg·mL^-1(r=0.9994)、0.125~7.5μg·mL^-1(r=0.9990)、0.160~10.43μg·mL^-1(r=0.9993),日内与日间精密度RSD均≤10.00%,提取回收率均≥85.00%。生品、酒品、醋品中五味子甲素、五味子乙素、五味子醇甲的Cmax分别为(1.087±0.23)、(2.221±0.366)、(0.914±0.18)mg·L^-1;(1.067±0.162)、(2.25±0.293)、(1.171±0.28)mg·L^-1;(4.95±0.655)、(6.349±0.679)、(3.347±0.693)mg·L^-1。AUC(0-t)分别为(15.54±3.41)、(26.84±5.23)、(12.12±0.96)mg·h·L^-1;(12.11±2.04)、(26.90±2.76)、(10.55±1.34)mg·h·L^-1;(45.79±4.61)、(60.97±6.42)、(30.64±5.13)mg·h·L^-1。结论该方法专属性强、灵敏度高、快速准确。酒五味子中3种木脂素在血浆中的含量均高于生品和醋品,可从药动学角度为酒五味子“入补药熟用”提供依据。
Objective Comparing the pharmacokinetic characteristics of three lignans in rats’plasma using a sensitive and reliable UPLC-MS/MS method,to provide a pharmacokinetic basis for the wine-processed Schisandrae chinensis fructus(CMF)as a tonic.Methods Eighteen rats were equally randomized into 3 groups,including the raw CMF group,wine CMF group and vinegar CMF group.Rats in each group were given decoction of corresponding CMF(a dose of 2 g·kg^-1)by gastrogavage,arctigenin was used as the internal standard and the plasma samples were pretreated with methanol.The UPLC-MS/MS set under the positive electrospray ionization mode,coupled with multiple reaction monitoring mode was used to analyze the concentrations of Deoxyschizandrin,γ-Schisandrin and Schisandrin in rats’plasma at different time points.The plasma drug concentration-time was fitted by DAS3.2.7 software to calculate its pharmacokinetic parameters.Results The calibration curves were linear within the ranges of 0.180-12.625μg·mL^-1(r=0.9994),0.125-7.50μg·mL^-1(r=0.9990)and 0.160-10.43μg·mL^-1(r=0.9993)for Deoxyschizandrin,γ-Schisandrin and Schisandrin,respectively.The relative standard deviations of the intraand inter-day precisions of the three compounds were less than 10%,and the extraction recoveries were more than 85.00%.The mean Cmax values of Deoxyschizandrin,γ-Schisandrin and Schisandrin in raw CMF,wine-processed CMF and vinegar-processed CMF were(1.087±0.23),(2.221±0.366),(0.914±0.18)mg·L^-1;(1.067±0.162),(2.25±0.293),(1.171±0.28)mg·L^-1;(4.95±0.655),(6.349±0.679),(3.347±0.693)mg·L^-1,respectively.The AUC(0-t)values were(15.54±3.41),(26.84±5.23),(12.12±0.96)mg·h·L^-1;(12.11±2.04),(26.90±2.76),(10.55±1.34)mg·h·L^-1;(45.79±4.61),(60.97±6.42),(30.64±5.13)mg·h·L^-1,respectively.Conclusion The method was specific,highly sensitive and accurate.The results showed that the wineprocessed CMF increased maximum plasma concentration most significantly,it provides a pharmacokinetic explanation for the wine-processed CMF as a tonic.
作者
庞博
赵芷含
单国顺
贾天柱
高慧
PANG Bo;ZHAO Zhihan;SHAN Guoshun;JIA Tianzhu;GAO Hui(College of Pharmacy,Liaoning University of TCM,Dalian 116600 Liaoning,China;Key Lab of Processing Principle Analysis State Administration of Traditional Chinese Medicine,Dalian 116600 Liaoning,China;Liaoning Research Center of Processing Engineering Technology for TCM,Dalian 116600 Liaoning,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2019年第11期1362-1367,共6页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
辽宁省中医药管理局项目（CCJDXM 2018-03）
国家发改委中医药行业专项（2110700704）
关键词
五味子
酒制
醋制
木脂素
UPLC-MS/MS法
药代动力学
Schisandrae chinensis fructus
wine-processed
vinegar-processed
lignans
UPLC-MS/MS
pharmacokinetics
