Integrating qualitative and quantitative liquid chromatography/tandem massspectrometric analysis to support drug discovery

During the early phase of a drug discovery process, in order to facilitate the selection of drug candidates from a discovery research program, a liqui d chromatography tandem mass spectrometry (LC/MS/MS) strategy has been deve loped to assess the preliminary pharmacokinetics and metabolism of new drug entities, For pharmacokinetic studies using multiple reaction monitoring ( MRM), the parent drug concentration and its 'suspected' (predictable) metab olites were monitored in the biological samples simultaneously. For metabol ic identification, the general methodologies most frequently used to search for metabolites include full scan, precursor-ion scan, product-ion scan an d neutral-loss scan, However, when the metabolites do not produce intense s ignals for tandem mass spectrometry, a more sensitive and selective assay h as to be developed, and MRM would be the method of choice. Likewise, an int elligent guess as to which MRM transitions ought to be used for the metabol ites will be considered, based on the product ion mass spectrum of the pare nt drug. Copyright (C) 1999 John Wiley & Sons, Ltd.