整合定性策略用于大黄素代谢物的高通量靶向鉴定  

Integrated Qualitative Strategy for High-throughput Targeted Filtering of Emodin Metabolites

作　　者：蔡芳 任繁栋 任达兵 刘韶[2] 易伦朝 CAI Fang;REN Fan-Dong;REN Da-Bing;LIU Shao;YI Lun-Zhao(Food Safety Research Institute,Kunming University of Science and Technology,Kunming 650504,China;Department of Pharmacy,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]昆明理工大学食品安全研究院,昆明650504 [2]中南大学湘雅医院药学部,长沙410008

出　　处：《分析化学》2019年第8期1212-1218,I0015-I0018,共11页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(No.21775058)资助~~

摘　　要：采用超高效液相色谱-四极杆-轨道阱质谱联用技术,使用Thermo scientific Hypersil GLOD色谱柱,以0.1%甲酸-乙腈为流动相,应用梯度洗脱程序对肾间质纤维化大鼠血清中的大黄素及其代谢物进行了分析。将质量亏损、中性丢失、诊断碎片离子过滤等技术互相融合,提出了一种可高通量靶向鉴定药物有效成分在体内的代谢物的方法,并将本方法应用到大黄素大鼠血液代谢物的鉴定中,鉴定出大黄素在大鼠体内的11种代谢物及39种可能的代谢物,并证明大黄素在大鼠体内的Ι相代谢途径主要是氧化和羟基化,Ⅱ相代谢途径主要是硫酸酯化和葡萄糖醛酸化。本方法有效减少了定性分析过程中基质和干扰离子的影响,提高了代谢物定性分析的效率和准确性。The emodin and its metabolites in serum of renal interstitial fibrosis rats were separated on a Thermo Scientific Hypersil GLOD column with the mixture of 0.1%formic acid water and acetonitrile as the mobile phase,and then analyzed by ultra-high performance liquid chromatography-high resolution mass spectrometry(UPLC-HRMS).In this study,an integrated qualitative strategy was proposed to identify the target metabolites of active pharmaceutical ingredients in vivo,which combined mass defect,neutral loss,and diagnostic fragment ion filtering.The method was applied to the identification of metabolites of emodin in rat blood,and 11 metabolites were determined accurately,39 possible metabolites were tentatively identified.The result shows that the metabolism pathways of emodin in rats were mainly oxidation and hydroxylation in phaseΙ,and sulfation and glucuronidation in phase II.The integrated qualitative strategy proposed here could effectively reduce matrix interference and interfering ions in the qualitative process,thus improveing the efficiency and accuracy of qualitative analysis of metabolites.

关 键 词：超高效液相色谱-高分辨质谱联用技术 质量亏损 诊断碎片离子 中性丢失 大黄素 

分 类 号：R28[医药卫生—中药学]