LC-MS-based metabolomics in drug metabolism.
Xenobiotic metabolism, a ubiquitous natural response to foreign compounds, elicits initiating signals for many pathophysiological events. Currently, most widely used techniques for identifying xenobiotic metabolites and metabolic pathways are empirical and largely based on in vitro incubation assays and in vivo radiotracing experiments. Recent work in our lab has shown that LC-MS-based metabolomic techniques are useful tools for xenobiotic metabolism research since multivariate data analysis in metabolomics can significantly rationalize the processes of xenobiotic metabolite identification and metabolic pathway analysis. In this review, the technological elements of LC-MS-based metabolomics for constructing high-quality datasets and conducting comprehensive data analysis are examined. Four novel approaches of using LC-MS-based metabolomic techniques in xenobiotic metabolism research are proposed and illustrated by case studies and proof-of-concept experiments, and the perspective on their application is further discussed.
Chen
Chi
C
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Gonzalez
Frank J
FJ
Idle
Jeffrey R
JR
D000818:Animals; D030801:Animals, Genetically Modified; D001711:Biotransformation; D002853:Chromatography, Liquid; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D015262:Xenobiotics / Q000378:metabolism