ABSTRACT
The complexity of the metabolite identication process is variable, depending on the nature of the sample matrix, the extent of the metabolism, the physicochemical properties of the drugs and their metabolites, and the dose administered. In addition, the level of information required is also variable. At its simplest, it may be sufcient to provide some idea of the metabolic vulnerability of the drug using in vitro screens, and, at its most complex, denitive metabolite structures will be elucidated and quantied using radiochemical techniques or bespoke quantitative metabolite assays. The former is generally used at the drug discovery stage, when it may be necessary to rank potential drug candidates according to their metabolic stability before candidate selection. During drug development, any preliminary metabolism work carried out at the discovery stage is expanded using tailored methods and radiolabelled drug. Here, the emphasis is on the determination of the denitive metabolism in the species used in the toxicological assessment, human predictions using in vitro techniques and, nally, unequivocal identication of metabolites following administration to human volunteers. This work forms part of the regulatory ling for the drug.
