基于UHPLC-Q-Orbitrap HRMS技术的白术内酯I在大鼠体内代谢产物的鉴定及代谢途径分析  

Metabolites and metabolic pathway analysis of atractylenolide I in rats based on UHPLC-Q-Orbitrap HRMS

作　　者：周胜楠 吴宿慧[1] 孙志[2,3] 包晓悦 王靖 李晓静 王霞[1] 李根林 ZHOU Shengnan;WU Suhui;SUN Zhi;BAO Xiaoyue;WANG Jing;LI Xiaojing;WANG Xia;LI Genlin(Henan University of Chinese Medicine,Zhengzhou 450046,China;Department of Pharmacy,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine,Zhengzhou 450052,China)

机构地区：[1]河南中医药大学,河南郑州450046 [2]郑州大学第一附属医院药学部,河南郑州450052 [3]河南省精准医学临床质谱工程研究中心,河南郑州450052

出　　处：《沈阳药科大学学报》2023年第11期1439-1448,1557,共11页Journal of Shenyang Pharmaceutical University

基　　金：河南省中医药科学研究专项(20-21ZY1037);河南省中青年卫生健康科技创新人才培养“优青人才”(YXKC2020058)。

摘　　要：目的采用超高效液相色谱-四级杆/静电场轨道阱高分辨质谱技术(UHPLC-Q-Orbitrap HRMS)鉴定白术内酯I在大鼠体内的代谢产物,并探讨其可能的代谢途径。方法SD大鼠单次灌胃给予白术内酯I后,收集大鼠血浆、尿液、粪便样品。以体积分数0.1%甲酸水溶液(A)-乙腈(B)为流动相,梯度洗脱。在电喷雾电离源(ESI源)正、负离子模式下分析大鼠生物样本。根据质谱提供的准分子离子峰、碎片离子及准确相对分子质量,鉴定白术内酯I体内代谢产物。结果共鉴定出大鼠体内代谢产物30个,其中血浆样品中5个,尿液样品中17个,粪便样品中16个。氧化、水合、脱饱和、硫酸化、葡萄糖醛酸化、甘氨酸结合、半胱氨酸结合等是白术内酯I体内主要的代谢途径。结论首次阐明了白术内酯I在大鼠体内的代谢产物及代谢途径,为其进一步的药效学评价和开发利用提供参考,此外也为单体药物代谢产物鉴定提供了一种综合研究方法。Objective To identify the metabolites of atractylenolide I and to explore its potential metabolic pathways in rats by using UHPLC-Q-Orbitrap HRMS technology.Methods The plasma,urine and feces samples were collected and processed after intragastric administration of atractylenolide I.The 0.1%formic acid water(A)-acetonitrile(B)were as the mobile phase with gradient elution.The biological samples of rats were analyzed under positive and negative ion modes of electrospray ionization(ESI)source.The metabolites of atractylodes I in vivo were identified according to the excimer ion peak,fragment ion and accurate relative molecular mass provided by mass spectrometry.Results A total of 30 metabolites of atractylenolide I were identified in rats,including 5 metabolites in plasma,17 metabolites in urine,and 16 metabolites in feces.It is speculated that the main metabolic reactions of atractylenolide I in rats were oxidation,hydration,desaturation,sulfuration,glucuronide conjugation,glycine conjugation,cysteine conjugation,and so on.Conclusion In this study,the metabolic process and metabolites of atractylenolide I are elucidated in the first time,which can provide reference for the further pharmacodynamic evaluation and utilization.In addition,it also provides a comprehensive method for the identification of individual drug metabolites.

关 键 词：白术内酯I UHPLC-Q-Orbitrap HRMS 代谢产物 代谢途径 

分 类 号：R917[医药卫生—药物分析学]