6533b82dfe1ef96bd12915e0
RESEARCH PRODUCT
Charged Tags for the Identification of Oxidative Drug Metabolites Based on Electrochemistry and Mass Spectrometry
Siegfried R. WaldvogelNadine PeezThorsten HoffmannAlexandra GutmannLars Julian Wesenbergsubject
Spectrometry Mass Electrospray IonizationAlkylationPyridinesElectrospray ionizationPyridinium CompoundsMass spectrometryHydroxylationlcsh:Chemistrydrug metabolitesCytochrome P-450 Enzyme Systemcharged tagsChromatography High Pressure Liquidmass spectrometrychemistry.chemical_classificationActive ingredientChromatographybiologyCommunicationanodic oxidationCytochrome P450General ChemistryMetabolismElectrochemical TechniquesMonooxygenaseCommunicationsEnzymelcsh:QD1-999chemistryelectrochemistrybiology.proteinOxidation-ReductionDrug metabolismMetoprololSignal Transductiondescription
Abstract 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-05-01 | ChemistryOpen |