Charged Tags for the Identification of Oxidative Drug Metabolites Based on Electrochemistry and Mass Spectrometry.
Alkylation
Chromatography, High Pressure Liquid
Cytochrome P-450 Enzyme System
/ metabolism
Electrochemical Techniques
Hydroxylation
Metoprolol
/ chemistry
Oxidation-Reduction
Pyridines
/ chemistry
Pyridinium Compounds
/ analysis
Signal Transduction
Spectrometry, Mass, Electrospray Ionization
/ methods
anodic oxidation
charged tags
drug metabolites
electrochemistry
mass spectrometry
Journal
ChemistryOpen
ISSN: 2191-1363
Titre abrégé: ChemistryOpen
Pays: Germany
ID NLM: 101594811
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
27
03
2020
entrez:
9
5
2020
pubmed:
10
5
2020
medline:
10
5
2020
Statut:
epublish
Résumé
Most of the active pharmaceutical ingredients like Metoprolol are oxidatively metabolized by liver enzymes, such as Cytochrome P450 monooxygenases into oxygenates and therefore hydrophilic products. It is of utmost importance to identify the metabolites and to gain knowledge on their toxic impacts. By using electrochemistry, it is possible to mimic enzymatic transformations and to identify metabolic hot spots. By introducing charged-tags into the intermediate, it is possible to detect and isolate metabolic products. The identification and synthesis of initially oxidized metabolites are important to understand possible toxic activities. The gained knowledge about the metabolism will simplify interpretation and predictions of metabolitic pathways. The oxidized products were analyzed with high performance liquid chromatography-mass spectrometry using electrospray ionization (HPLC-ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy. For proof-of-principle, we present a synthesis of one pyridinated main oxidation product of Metoprolol.
Identifiants
pubmed: 32382470
doi: 10.1002/open.202000084
pii: OPEN202000084
pmc: PMC7202420
doi:
Substances chimiques
Pyridines
0
Pyridinium Compounds
0
Cytochrome P-450 Enzyme System
9035-51-2
Metoprolol
GEB06NHM23
pyridine
NH9L3PP67S
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
568-572Informations de copyright
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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