During the early phase of a drug discovery process, in order to facilitate the selection of drug candidates from a discovery research program, a liquid chromatography tandem mass spectrometry (LC/MS/MS) strategy has been developed 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) metabolites were monitored in the biological samples simultaneously. For metabolic identification, the general methodologies most frequently used to search for metabolites include full scan, precursor-ion scan, product-ion scan and neutral-loss scan. However, when the metabolites do not produce intense signals for tandem mass spectrometry, a more sensitive and selective assay has to be developed, and MRM would be the method of choice. Likewise, an intelligent guess as to which MRM transitions ought to be used for the metabolites will be considered, based on the product ion mass spectrum of the parent drug.
Copyright 1999 John Wiley & Sons, Ltd.