Systematic and comprehensive strategy for metabolite profiling in bioanalysis using software-assisted HPLC-Q-TOF: magnoflorine as an example

doi:10.1007/s00216-015-9254-5

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	Systematic and comprehensive strategy for metabolite profiling in bioanalysis using software-assisted HPLC-Q-TOF: magnoflorine as an example
	Tian, Xiaoting; Zhang, Yucheng; Li, Zhixiong; Hu, Pei; Chen, Mingcang; Sun, Zhaolin; Lin, Yunfei; Pan, Guoyu; Huang, Chenggang
刊名	ANALYTICAL AND BIOANALYTICAL CHEMISTRY
	2016-03
卷号	408 期号:9 页码:2239-2254
关键词	Magnoflorine High resolution LC-Q-TOF Metabolite ID Metabolites
ISSN号	1618-2642
DOI	10.1007/s00216-015-9254-5
文献子类	Article
英文摘要	Metabolite profiling plays a crucial role in drug discovery and development, and HPLC-Q-TOF has evolved into a powerful and effective high-resolution analytical tool for metabolite detection. However, traditional empirical identification is laborious and incomplete. This paper presents a systematic and comprehensive strategy for elucidating metabolite structures using software-assisted HPLC-Q-TOF that takes full advantage of data acquisition, data processing, and data mining technologies, especially for high-throughput metabolite screening. This strategy has been successfully applied in the study of magnoflorine metabolism based on our previous report of its poor bioavailability and drug-drug interactions. In this report, 23 metabolites of magnoflorine were tentatively identified with detailed fragmentation pathways in rat biological samples (urine, feces, plasma, and various organs) after i.p. or i.g. administration, and for most of these metabolites, the metabolic sites were determined. The phase I biotransformations of magnoflorine (M1-M7, M10-M14) consist of demethylation, dehydrogenation, hydroxylation, methylene to ketone transformation, N-ring opening, and dehydroxylation. The phase II biotransformations (M8, M9, and M15-M23) consist of methylation, acetylation, glucuronidation, and N-acetylcysteine conjugation. The results indicate that the extensive metabolism and wide tissue distribution of magnoflorine and its metabolites may partly contribute to its poor bioavailability and drug-drug interaction, and i.p. administration should thus be a suitable approach for isolating magnoflorine metabolites. In summary, this strategy could provide an efficient, rapid, and reliable method for the structural characterization of drug metabolites and may be applicable for general Q-TOF users.
资助项目	National Science Foundation of China[81030065] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2009ZX09102-121] ; National Natural Science Funds for Distinguished Young Scholar[813028361009936] ; National High Technology Research and Development Program of China[2013AA032202] ; Leading Science and Technology Projects[XDA01030600]
WOS关键词	FLIGHT MASS-SPECTROMETRY ; APORPHINE ALKALOIDS ; TINOSPORA-CORDIFOLIA ; DRUG-METABOLISM ; PHASE-1 METABOLITES ; COPTIDIS-RHIZOMA ; RAT URINE ; IDENTIFICATION ; CONSTITUENTS ; BERBERINE
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	SPRINGER HEIDELBERG
WOS记录号	WOS:000372598600006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276120]
专题	药物安全性评价中心上海中药现代化研究中心
通讯作者	Pan, Guoyu; Huang, Chenggang
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Tian, Xiaoting,Zhang, Yucheng,Li, Zhixiong,et al. Systematic and comprehensive strategy for metabolite profiling in bioanalysis using software-assisted HPLC-Q-TOF: magnoflorine as an example[J]. ANALYTICAL AND BIOANALYTICAL CHEMISTRY,2016,408(9):2239-2254.
APA	Tian, Xiaoting.,Zhang, Yucheng.,Li, Zhixiong.,Hu, Pei.,Chen, Mingcang.,...&Huang, Chenggang.(2016).Systematic and comprehensive strategy for metabolite profiling in bioanalysis using software-assisted HPLC-Q-TOF: magnoflorine as an example.ANALYTICAL AND BIOANALYTICAL CHEMISTRY,408(9),2239-2254.
MLA	Tian, Xiaoting,et al."Systematic and comprehensive strategy for metabolite profiling in bioanalysis using software-assisted HPLC-Q-TOF: magnoflorine as an example".ANALYTICAL AND BIOANALYTICAL CHEMISTRY 408.9(2016):2239-2254.