Study of the Distribution of Acetaminophen and Its Metabolites in Rats, from the Whole-Body to Isolated Organ Levels, by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging after On-Tissue Chemical Derivatization - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Analytical Chemistry Année : 2021

Study of the Distribution of Acetaminophen and Its Metabolites in Rats, from the Whole-Body to Isolated Organ Levels, by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging after On-Tissue Chemical Derivatization

Résumé

During drug development, detailed investigations of the pharmacokinetic profile of the drug are required to characterize its absorption, distribution, metabolism, and excretion properties. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is an established technique for studies of the distribution of drugs and their metabolites. It has advantages over autoradiography, which is conventionally used for distribution studies: it does not require the radiolabeling of drugs and can distinguish between the drug and its metabolites directly in the tissue. However, its lack of sensitivity in certain cases remains challenging. Novel procedures, such as on-tissue chemical derivatization (OTCD), could be developed to increase sensitivity. We used OTCD to enhance the sensitivity of MALDI-MSI for one of the most widely used drugs, acetaminophen, and to study its distribution in tissues. Without derivatization, this drug and some of its metabolites are undetectable by MALDI-MSI in the tissues of treated rats. We used 2-fluoro-1-methylpyridinium p-toluene sulfonate as a derivatization reagent, to increase the ionization yield of acetaminophen and some of its metabolites. The OTCD protocol made it possible to study the distribution of acetaminophen and its metabolites in whole-body sections at a spatial resolution of 400 μm and in complex anatomical structures, such as the testis and epididymis, at a spatial resolution <50 μm. The OTCD is also shown to be compatible with the quantification of acetaminophen by MALDI-MSI in whole-body tissues. This protocol could be applied to other molecules bearing phenol groups and presenting a low ionization efficiency.
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hal-03368218 , version 1 (06-10-2021)

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Mira Merdas, Mélanie Lagarrigue, Thierry Umbdenstock, Antoine Lhumeau, Françoise Dartiguelongue, et al.. Study of the Distribution of Acetaminophen and Its Metabolites in Rats, from the Whole-Body to Isolated Organ Levels, by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging after On-Tissue Chemical Derivatization. Analytical Chemistry, 2021, 93 (39), pp.13242-13250. ⟨10.1021/acs.analchem.1c02487⟩. ⟨hal-03368218⟩
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