title: Nuclear magnetic resonance (NMR)-based drug metabolite profiling.
abstract: The identification of drug metabolites in biofluids such as urine, plasma and bile is an important step in drug discovery and development. Proton nuclear magnetic resonance ((1)H-NMR) spectroscopy can provide detailed information regarding the structural transformation of a compound as a consequence of metabolism. However, successful identification of drug metabolites by (1)H-NMR spectroscopy is generally compromised by the presence of endogenous metabolites, which can obscure the signals of the drug metabolites in question. Hence, sample clean-up and separation of the metabolites from the biofluid matrix is crucial. This is generally achieved by extraction of the biofluid, solid-phase extraction (SPE), high-performance liquid chromatography (HPLC) or any combination of these. Apart from (1)H, other NMR-active nuclei, such as (19)F, can provide a useful handle for metabolite profiling, provided they are not naturally present in the biofluid. Successful studies have shown that the presence of a fluorine-handle on the drug and its metabolites can provide additional qualitative and quantitative data by (19)F-NMR spectroscopy. This chapter provides guidelines and examples of NMR-based drug metabolite profiling.
authors.affiliation: AstraZeneca Pharmaceuticals, Mereside, Macclesfield, UK. eva.lenz@astrazeneca.com
authors.forename: Eva M
authors.initials: EM
authors.lastname: Lenz
mesh_terms: D053000:Analytic Sample Preparation Methods; D001647:Bile Acids and Salts / Q000737:chemistry; D001798:Blood Proteins / Q000737:chemistry; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D019963:Clinical Chemistry Tests; D005612:Freeze Drying; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D052616:Solid Phase Extraction
chemical_list: D001647:Bile Acids and Salts; D001798:Blood Proteins; D004364:Pharmaceutical Preparations