液相色谱-质谱联用技术在药物代谢产物鉴定中的应用

发布时间：2018-02-01 01:28

本文关键词： 液相色谱-质谱(LC/MS) 代谢产物鉴定反应性代谢产物高分辨质谱(HRMS)　出处：《质谱学报》2017年04期 　论文类型：期刊论文

【摘要】：药物代谢研究贯穿药物开发的整个过程。生物基质中药物代谢产物的快速、准确鉴定有助于理解药物或候选化合物的生物转化途径,确定代谢软位点,从而帮助优化先导物结构,筛选出具有更高代谢稳定性的药物。利用亲核性捕获试剂开展体外代谢实验,检测反应性代谢产物的生成,相关结果可以帮助规避候选化合物进入临床后可能产生的毒性风险。由于液相色谱-质谱联用技术(LC/MS)具有分析通量高、检测灵敏度高、选择性好、能提供丰富的结构相关信息等优点,其在药物代谢研究中的作用越来越重要。本工作综述了近年来作者所在实验室采用LC/MS法开展的药物代谢产物鉴定研究,提出了基于LC/MS技术的药物代谢产物鉴定研究的基本流程和药物在人体内的主要代谢产物,可为临床药动学研究和药物相互作用研究提供数据基础。
[Abstract]:Drug metabolism research runs through the whole process of drug development. The rapid and accurate identification of drug metabolites in biological matrix is helpful to understand the biotransformation pathway of drugs or candidate compounds and to identify the soft sites of metabolism. In order to help optimize the structure of the guide, screening out the drug with higher metabolic stability, using nucleophilic capture reagent to carry out in vitro metabolism experiments, to detect the formation of reactive metabolites. The results can help to avoid the potential toxicity risk after candidate compounds enter the clinic. Because of the high analytical throughput, high detection sensitivity and good selectivity, the liquid chromatography-mass spectrometry (LC-MS) combined with LCP-MS has the advantages of high analytical throughput, high detection sensitivity and good selectivity. Can provide rich structure related information and other advantages. It is more and more important in the study of drug metabolism. This paper reviews the recent studies on the identification of drug metabolites carried out by LC/MS method in our laboratory. The basic process of drug metabolites identification based on LC/MS technology and the main metabolites of drugs in human body are put forward, which can provide the data basis for clinical pharmacokinetics and drug interaction research.
【作者单位】：中国科学院上海药物研究所药物代谢研究中心;
【分类号】：O657.63;R965
【正文快照】： 药物的吸收、分布、代谢和排泄(ADME)性质影响其成药性、有效性和安全性,药物代谢研究是药物研发过程中的重要环节和内容,贯穿药物发现和开发的全过程,是决定药物是否能上市的关键因素之一。药物代谢产物的追踪和结构鉴定是创新药物ADME试验的核心内容之一,也是药物代谢研究的

【相似文献】