UHPLC-QTOF-MS法分析鉴定止咳宝片在大鼠血浆中的代谢产物  

Identification of major bioactive components and their metabolites in rat plasma after oral administration of Zhikebao tablet by UHPLC-QTOF-MS

作　　者：乔湜[1] 许海山[1] 石晓伟[2] 王伟[1] 李清艳[1] QIAO Shi;XU Hai-shan;SHI Xiao-wei;WANG Wei;LI Qing-yan(Civil Aviation Medical Center,Civil Aviation Administration of China（Civil Aviation General Hospital）,Beijing 100123,China;School of Pharmacy,Hebei Medical University,Shijiazhuang 050017,China)

机构地区：[1]中国民用航空局民用航空医学中心(民航总医院),北京100123 [2]河北医科大学药学院,河北石家庄050017

出　　处：《药学学报》2018年第9期1536-1544,共9页Acta Pharmaceutica Sinica

基　　金：民航安全能力建设基金资助项目(DFS20160604)

摘　　要：采用UHPLC-QTOF-MS技术分析大鼠灌胃给予止咳宝片后的血浆生物样本。首先,在正、负离子模式下分别全扫描,通过信息依赖采集触发子离子的采集,每一循环采集8个最强峰的二级质谱图。采集时进行,实时多重质量亏损和动态背景扣除。其次,应用Metabolite Pilot 2.0软件对止咳宝片君药罂粟壳,配伍药物甘草中主要化学成分为目标建立分析模型,分析各成分的保留时间、精确分子质量、二级质谱信息,对代谢产物进行解析。鉴定5个阿片类生物碱、甘草苷和甘草酸,及其相关代谢产物31个。5种阿片类生物碱、甘草苷和甘草酸在大鼠体内的代谢途径包括葡萄糖醛酸化、硫酸化、脱甲基化、脱氨基甲基后羧基化、水解等。本文从定性角度对复方中药制剂中主要活性成分的体内代谢开展研究,并与已有单一化学药物代谢途径比较,为进一步阐明止咳宝片或含罂粟壳、甘草类复方中药制剂体内代谢过程提供基础。An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry（UHPLC-Q-TOF/MS） method was established to identify the metabolites in rat plasma after oral administration of Zhikebao tablets. The high-resolution mass spectrometer was operated in positive and negative ion mode, respectively. First, full-scan was applied, which was dependent on a multiple mass defect filter（MMDF） combined with dynamic background subtraction（DBS）. These were utilized to trigger the information dependent acquisition（IDA） function in the experiment. For the IDA criteria, the eight most intense candidate ions of per cycle were selected to do a product ion scan. Then Metabolite Pilot 2.0 software was utilized to load data to seek possible metabolites. The analytical models employed by Metabolite pilot 2.0 were established for representative compounds of the Papaveris Pericarpium and licorice in Zhikebao tablet. Finally, metabolites were identified according to accurate mass measurement and retention time. 38 components from the rat plasma after oral administration of the drug have been found, including 5 prototype opium alkaloids, liquiritin, glycyrrhizic acid and 31 relative metabolites. The metabolic transformation of Zhikebao tablet in rats was mainly induced by glucuronidation, sulfation, methylation, amine to carboxylic acid, hydrolysis and so on. In this paper, the metabolites of the main active components of Zhikebao tablet were tentatively identified, and the metabolic pathway was compared with that of single chemical drugs. Moreover, it laid the fundamental elucidation of further metabolism study of Zhikebao tablet or other compound traditional Chinese medicine preparations which containing Papaveris Pericarpium or licorice.

关 键 词：止咳宝片 罂粟壳 UHPLC-QTOF-MS 代谢产物 阿片类生物碱 甘草 

分 类 号：R917[医药卫生—药物分析学]