Application of LC-high-resolution MS with “intelligent” data mining tools for screening reactive Drug metabolites

Department of Drug Metabolism and Pharmacokinetics, Genentech, Inc., South San Francisco, CA, USA.
Bioanalysis (Impact Factor: 3). 03/2012; 4(5):501-10. DOI: 10.4155/bio.12.5
Source: PubMed

ABSTRACT Biotransformation of chemically stable compounds to reactive metabolites that can bind covalently to macromolecules (such as proteins and DNA) is considered an undesirable property of drug candidates. Due to the possible link, which has not yet been conclusively demonstrated, between reactive metabolites and adverse drug reactions, screening for metabolic activation of lead compounds through in vitro chemical trapping experiments has become an integral part of the drug discovery process in many laboratories. In this review, we provide an overview of the recent advances in the application of high-resolution MS. These advances facilitated the development of accurate-mass-based data mining tools for high-throughput screening of reactive drug metabolites in drug discovery.

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    ABSTRACT: This chapter contains sections titled: Introduction In Vitro Trapping of Reactive Metabolites Traditional Liquid Chromatography-Tandem Mass Spectrometry (LC/MS/MS) Approaches for Reactive Metabolite Screening HRMS Accurate Mass-Based Data Mining Tools for Screening Reactive Metabolites Quantitation of Reactive Metabolite Formation Challenges and Future Perspectives References
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    Analytical Chemistry 01/2014; 86(2). DOI:10.1021/ac403385y · 5.64 Impact Factor
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