MS in early pharmacokinetics

In-vitro Microsomal Stability Screen Caco-2 Absorption Screen P450 Enzyme Inhibition Screen Rapid Rat (CARRS) PO/PK Screen 

Rat/Dog/Monkey IV / PO Initial Full PK Studies Discovery Metabolite ID Studies Special PK Studies and Other Pre-Development Tests 

From a DMPK perspective, a common goal is to be able to compare multiple compounds based on their absorption, distribution, metabolism and excretion (ADME) properties as well their preclinical PK properties [8, 12-22]. Therefore, lead optimization typically is performed as an iterative process that uses the DMPK data to select structural modifications that are then tested to see whether the DMPK properties of the series have been improved. This iterative process is shown schematically in Fig. 13.2. Clearly an important element for the successful lead optimization of a series of NCEs is the ability to perform the DMPK assays in a higher throughput manner. The focus of this chapter will be to discuss ways that mass spectrometry (MS), particularly HPLC-MS/MS can be used to support the early PK studies for NCEs in a higher throughput manner. 

HPLC-MS/MS has been described as the premier analytical tool for drug metabolism participation in the new drug discovery process and has been applied to a 

Fuller profile for selected compounds (tn silico, in vitrn, in vivo) 

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