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- W2034953536 abstract "Biotransformation of chemically stable compounds to reactive metabolites which can bind covalently to macromolecules, such as proteins and DNA, is considered as an undesirable feature of drug candidates. As part of an overall assessment of absorption, distribution, metabolism and excretion (ADME) properties, many pharmaceutical companies have put methods in place to screen drug candidates for their tendency to generate reactive metabolites and as well characterize the nature of the reactive metabolites through in vitro and in vivo studies. After identification of the problematic compounds, steps can be taken to minimize the potential of bioactivation through appropriate structural modifications. For these reasons, detection, structural characterization and quantification of reactive metabolites by mass spectrometry have become an important task in the drug discovery process. Triple quadrupole mass spectrometry is traditionally employed for the analysis of reactive metabolites. In the past 3 years, a number of new mass spectrometry methodologies have been developed to improve the sensitivity, selectivity and throughput of the analysis. This review focuses on the recent advances in the detection and characterization of reactive metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in drug discovery and development, especially through the use of linear ion trap (LTQ), hybrid triple quadrupole-linear ion trap (Q-trap) and the high resolution LTQ-Orbitrap instruments." @default.
- W2034953536 created "2016-06-24" @default.
- W2034953536 creator A5002921341 @default.
- W2034953536 creator A5062756879 @default.
- W2034953536 date "2009-04-01" @default.
- W2034953536 modified "2023-10-14" @default.
- W2034953536 title "Recent advances in applications of liquid chromatography–tandem mass spectrometry to the analysis of reactive drug metabolites" @default.
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- W2034953536 doi "https://doi.org/10.1016/j.cbi.2008.09.014" @default.
- W2034953536 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18848531" @default.
- W2034953536 hasPublicationYear "2009" @default.
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