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Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract

查看全文 作  者:Chenhui [1]Du;Yan [2]Yan;Chenxi [2]Shen;Xiaofang [1]Cui;Xiangping [1]Pei;Xuemei [2]Qin 高影响力作者 机构地区:[1]School of Chinese Materia Medica,Shanxi University of Chinese Medicine,Taiyuan,030619,China;[2]Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan,030006,China高影响力机构 出  处:《Journal of Pharmaceutical Analysis》索引2020年第10卷第4期,共11页高影响力期刊 基  金:This work was supported by grants from the National Natural Science Foundation of China(No:81603289,81603251);Key Laboratory of Effective Substances Research and Utilization in TCM of Shanxi province(No:201605D111004);and Key Technology Research Zhen Dong Special Project from Shanxi Science and Technology Department(No:2016ZD0105). 摘  要:Ziziphi Spinosae Semen(ZSS),a traditional Chinese medicine,is used in clinics for the treatment of insomnia in China and other Asian countries.Herein,we described for the first time a comparative pharmacokinetics study of the six major compounds of ZSS in normal control(NC)and para-chlorophenylalanine(PCPA)-induced insomnia model(IM)rats that were orally administered the aqueous extract of ZSS.An ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass(UHPLC-Q-Orbitrap-MS)method was developed and validated for the simultaneous determination of coclaurine,magnoflorine,spinosin,6000-feruloylspinosin,jujuboside A(JuA),and jujuboside B(JuB)in ZSS in rat plasma.The established approach was successfully applied to a comparative pharmacokinetic study.The systemic exposures of spinosin and 6000-feruloylspinosin were decreased in the IM group compared to the NC group,while plasma clearance(CL)was significantly increased.The Tmax values of JuA and JuB in IM rats were significantly lower than those in NC rats.The T1/2 of JuA in the IM group was significantly accelerated.The pharmacokinetic parameters of coclaurine and magnoflorine were not evidently affected between the two groups.These results indicate that the pathological state of insomnia altered the plasma pharmacokinetics of spinosin,6000-feruloylspinosin,JuA,and JuB in the ZSS aqueous extract,providing an experimental basis for the role of ZSS in insomnia treatment.The comparative pharmacokinetics-based UHPLC-Q-Orbitrap-MS using full-scan mode can therefore provide a reliable and suitable means for the screening of potentially effective substances applied as quality markers of ZSS. 关 键 词:Ziziphi Spinosae Semen PHARMACOKINETICS INSOMNIA UHPLC-Q-orbitrap-MS Six compounds
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