Abstract
Determination of metabolic stability and metabolite profiles of the new chemical entities (NCEs) plays a key role in the drug discovery and development process. At an early stage of drug discovery, information on the metabolic fate of the NCEs can direct medicinal chemists to synthesize metabolically more stable analogs by blocking sites of metabolism, and potentially creating NCEs with superior pharmacology and safety profiles. In the development stage, the focus is shifted to characterization of human metabolites, which enables the judicious selection of animal species used for safety evaluation and ensure that the selected animal species are exposed to all major metabolites formed in humans. The traditional method for metabolite characterization, HPLC-MS, requires extensive sample preparation prior to analysis. A correctly selected processing method results in cleaner samples, less background, and easier data interpretation. This chapter covers various aspects of sample preparation for studying metabolism of the drug candidates. An overview of the sample preparation approaches for both in vitro and in vivo studies including metabolic stability studies and screening for reactive metabolites is presented. Aspects of planning and conducting biotransformation in vivo studies starting from a sample collection, pooling, extracting drug-derived material are discussed. In addition, recommendations on how to investigate sample stability and to prevent degradation of metabolites are given.
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Penner, N., Das, B., Woodward, C., Prakash, C. (2011). Sample Preparation for Drug Metabolism Studies. In: Ivanov, A., Lazarev, A. (eds) Sample Preparation in Biological Mass Spectrometry. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0828-0_43
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DOI: https://doi.org/10.1007/978-94-007-0828-0_43
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