Mass Spectrometry Study about In Vitro and In Vivo Reaction between Metformin and Glucose: A Preliminary Investigation on Alternative Biological Behavior
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Published:2023-12-22
Issue:1
Volume:25
Page:180
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Bartolucci Gianluca1ORCID, Pallecchi Marco1ORCID, Braconi Laura1, Dei Silvia1ORCID, Teodori Elisabetta1ORCID, Lapolla Annunziata2, Sartore Giovanni2ORCID, Traldi Pietro3
Affiliation:
1. Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino (NEUROFARBA), Università di Firenze, 50100 Firenze, Italy 2. Dipartimento di Medicina, Università di Padova, 35100 Padova, Italy 3. Istituto di Ricerca Pediatrica Città della Speranza, 35100 Padova, Italy
Abstract
Metformin is the most prescribed glucose-lowering drug worldwide; globally, over 100 million patients are prescribed this drug annually. Some different action mechanisms have been proposed for this drug, but, surprisingly, no metabolite of metformin has ever been described. It was considered interesting to investigate the possible reaction of metformin with glucose following the Maillard reaction pattern. The reaction was first performed in in vitro conditions, showing the formation of two adducts that originated by the condensation of the two molecular species with the losses of one or two water molecules. Their structures were investigated by liquid chromatography coupled with mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS) and accurate mass measurements (HRMS). The species originated via the reaction of glucose and metformin and were called metformose and dehydrometformose, and some structural hypotheses were conducted. It is worth to emphasize that they were detected in urine samples from a diabetic patient treated with metformin and consequently they must be considered metabolites of the drug, which has never been identified before now. The glucose-related substructure of these compounds could reflect an improved transfer across cell membranes and, consequently, new hypotheses could be made about the biological targets of metformin.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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