Applications of Liquid Chromatography-Mass Spectrometry in Drug Metabolite Identification

doi:10.7538/zpxb.2016.0208

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	Applications of Liquid Chromatography-Mass Spectrometry in Drug Metabolite Identification
	Li, Liang; Chen, Xiao-Yan; Zhong, Da-Fang
刊名	Journal of Chinese Mass Spectrometry Society
	2017-07-01
卷号	38 期号:4 页码:375-387
ISSN号	10042997
DOI	10.7538/zpxb.2016.0208
文献子类	Article
英文摘要	Drug metabolism study is an integral part of drug discovery and development. Quick and accurate identification of the metabolites that formed in the biological matrix is crucial for the understanding of biotransformation pathways of drugs or drug candidates. Information on the metabolic soft sites of a candidate could help the optimization of the lead compound to screen drugs that have higher metabolic stability. On the other hand, the use of nucleophilic capture reagents to carry out in vitro metabolism studies to screen reactive metabolites could avoid the possible toxicity risks in clinical practice. Because of its high speed, high sensitivity, good selectivity, and the ability to provide rich structure-related informations, liquid chromatography-mass spectrometry (LC/MS) has become a dominant tool in drug metabolism studies. In recent ten years, metabolism studies on more than one hundred drugs, drug candidates, or natural active compounds have been carried out in our lab by either liquid chromatography/ion trap mass spectrometry (LC/MSn) or ultrahigh performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). At present, some drugs have either entered into clinical research or been approved for the treatment of multiple diseases by China Food and Drug Administration. This paper reviews the use of LC/MS in the drug metabolite identification studies in our lab, and offers thoughts on the general workflow for drug metabolite detection and structure elucidation using LC/MS. The workflow proposed in this review has focused on the metabolite identification studies on small-molecule xenobiotics. In addition, this review also discusses the advantages and disadvantages as well as the remaining challenges in drug metabolism and disposition studies using LC/MS technology. Principles of biological samples selection and preparation in drug metabolism studies has also been involved. In conclusion, the general workflow for small-molecule drug metabolism study using LC/MS has been proposed, which intends to provide a basis for clinical pharmacokinetics and drug-drug interaction studies.
语种	中文
CSCD记录号	CSCD:6030870
出版者	Chinese Society for Mass Spectrometry
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266955]
专题	上海药物代谢研究中心
通讯作者	Zhong, Da-Fang
作者单位	Center for Drug Metabolism and Pharmacokinetics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai; 201203, China
推荐引用方式 GB/T 7714	Li, Liang,Chen, Xiao-Yan,Zhong, Da-Fang. Applications of Liquid Chromatography-Mass Spectrometry in Drug Metabolite Identification[J]. Journal of Chinese Mass Spectrometry Society,2017,38(4):375-387.
APA	Li, Liang,Chen, Xiao-Yan,&Zhong, Da-Fang.(2017).Applications of Liquid Chromatography-Mass Spectrometry in Drug Metabolite Identification.Journal of Chinese Mass Spectrometry Society,38(4),375-387.
MLA	Li, Liang,et al."Applications of Liquid Chromatography-Mass Spectrometry in Drug Metabolite Identification".Journal of Chinese Mass Spectrometry Society 38.4(2017):375-387.