ANYL 245 |
| The concept that reactive drug metabolites could play a role in deleterious in-vivo toxicity events such as tissue necrosis, mutagenicity and teratogenicity is based on research conducted over the past three decades. Although there has yet to be identified a direct mechanistic link between reactive drug metabolite formation and the onset of certain toxicities, there exist a number of cases where the toxicity finding, especially those considered "idiosyncratic", is accompanied by reactive drug metabolite formation by the drug compound. Furthermore, there is mounting evidence to suggest that protein covalent binding brought about by the inadequate detoxification of reactive metabolites could be a precursor event in the mechanistic cascade leading to immune mediated toxicity in-vivo. This presentation will focus on three areas of reactive metabolite screening; (i) Overview and rationale for screening for reactive metabolites during early drug discovery, (ii) the high throughput, high compound capacity reactive metabolite assay currently used in our laboratory and (iii) development and use of a novel method to semi-quantitatively determine reactive metabolite conjugate levels as a follow-up "risk assessment" approach to our high throughput assay. |
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Methods Development for Pharmaceutical Analysis
1:30 PM-5:00 PM, Tuesday, 12 September 2006 Moscone Center -- Room 124, Oral
Division of Analytical Chemistry |