Drug reactive metabolite trapping

Utility of Reactive Metabolite Trapping and Covalent Binding Studies in Drug Discovery... 

ARE REACTIVE METABOLITE TRAPPING AND COVALENT BINDING STUDIES RELIABLE PREDICTORS OF TOXICITY POTENTIAL OF DRUG CANDIDATES ... 

The process for the identification of trapped reactive intermediates can be a slow, painstaking task. Strategies to screen for the occurrence of these reactive metabolites to increase the attrition of potentially toxic drugs can significantly reduce the cost of the development. Much of what follows in this chapter is focused on the development of such screening procedures. 

Baughman, T.M. Wells-Knecht, M. Wells-Knecht, K. Zhao, Z. Method Validation for a Glutathione-trapping Reactive Metabolite Assay Using Drugs with Structural Moieties Known to Produce Reactive Species, Drug Metab. Rev. 35(S2), 112 (2003). 

Most reactive metabolites are electrophiles that react with compounds that contain nitrogen or sulfur atoms. These reactive species are generally short-lived and highly unstable. Therefore, analysis and detection is challenging. The approach that is currently used to characterize reactive metabolites in drug discovery involves the use of trapping agents that form stable adducts with the reactive intermediates [95],... 

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