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Qualitative and quantitative determination of drugs, metabolites and their adducts to proteins in biological matrices by liquid chromatography hyphenated to low and high resolution mass spectrometry

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Defense Thèse de doctorat : Univ. Genève, 2012 - Sc. 4507 - 2012/10/29
Abstract The development of targeted and untargeted analytical methods to support metabolomics studies has generated a paradigm shift in bioanalysis. In particular, liquid chromatography hyphenated to mass spectrometry has demonstrated the capability to quantify and identify thousands of compounds in biological samples using different instruments. Until recently, low and high resolution mass spectrometers were concomitantly used to achieve these goals. The recent development of fast-acquiring and sensitive high resolution mass spectrometers has opened the door to efficient and simultaneous qualitative and quantitative data acquisition. The central theme of this thesis was the investigation of these novel tools applied to drug metabolism and toxicology. The study of the metabolism of fipexide, a nootropic hepatotoxic drug, is described. The quantitative determination of acetaminophen (paracetamol) and its metabolites along with the measure of its adducts to proteins combined with untargeted analysis is also presented within the frame of a clinical study with overdosed patients.
Keywords BioanalysisMass spectrometryMetabolismToxicologyAcetaminophenFipexideMetabolomicsQuantitationValidationQUAL/QUANSWATH
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URN: urn:nbn:ch:unige-263604
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TONOLI, David. Qualitative and quantitative determination of drugs, metabolites and their adducts to proteins in biological matrices by liquid chromatography hyphenated to low and high resolution mass spectrometry. Université de Genève. Thèse, 2012. https://archive-ouverte.unige.ch/unige:26360

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Deposited on : 2013-02-11

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