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Micropreparative isolation and NMR structure elucidation of metabolites of a drug candidate from rat bile and urine

Blanz, Joachim and Delemonte, Thierry and Pearson, David and Luneau, Alexandre and Ritzau, Michael and Gertsch, Werner and Ramstein, Philippe and Dayer, Jerome and Desrayaud, Sandrine and Braun, Elisabeth and Aichholz, Reiner (2015) Micropreparative isolation and NMR structure elucidation of metabolites of a drug candidate from rat bile and urine. Journal of Chromatography B: Biomedical Sciences and Applications, 989. pp. 1-10.

Abstract

LC-MS based drug metabolism studies are effective in the optimization stage of drug discovery for rapid partial structure identification of metabolites. However, these studies usually do not provide unambiguous structural characterization of all metabolites, due to the limitations of MS-based structure identification. LC-MS-SPE-NMR is a more powerful approach that allows complete structure identification of compounds from mixtures. LC-MS-SPE-NMR of compounds in complex in vivo samples (such as bile samples from drug metabolism studies) is difficult due to the presence of high concentrations of interfering endogenous components, and potentially also dosage vehicle components (e.g. polyethylene glycols). Here, we describe the isolation and structure characterization of seven metabolites of a drug development candidate in bile and urine samples from a routine low dose bile-duct cannulated rat metabolism study. The structure of all seven compounds could be determined, resulting in much higher information content than common LC-MS structure characterization studies.

Item Type: Article
Keywords: Biotransformation, metabolism, micropreparative isolation, bile, urine, mass spectrometry, NMR, Solid phase extraction, cryogenic NMR, HPLC, LC-MS, structure elucidation
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/23494

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