Speeding metabolic stability assays using automated high throughput LC/MS techniques

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Johnson, Kelly;Erve, John;Dandeneau, Andre;Kenney, Beverly
Poster Presentation 49th ASMS Conference on Mass Spectrometry - May, 2001
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Quinidine; Ketoconazole; Cytochromes P450; Propranolol
human liver microsomes
Symmetry® C18 3.5 µm Steel 4.6 mm 50 mm Symmetry® C18 3.5 µm Steel 2.1 mm 50 mm
In drug discovery, metabolic stability is often a key factor in whether or not a compound continues on in the development process. Metabolic stability can be assessed in vitro using pooled liver microsomes obtained from humans or other species of interest. To meet the growing demand for rapid analysis of the large number of samples generated by metabolic stability assays, automation has become necessary to increase sample analysis. The use of LC/MS analytical methods provides the required selectivity, sensitivity, and speed to produce quality data. This presentation will demonstrate the use of LC/MS to evaluate samples produced in a metabolic stability assay. Taking advantage of such factors as parallel sample processing, high sample capacity, alternating column regeneration, and smaller diameter columns to reduce cycle times, we can analyze the large number of samples produced, and ultimately help expedite the drug discovery process.

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