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Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics

In this study, the phase I hepatic metabolism pathway of a cardiovascular drug nebivolol was proposed on the basis of a human liver microsomes assay with the use of LC-HR-MS coupled with the chemometric method. Six biotransformation products were found with the assistance of chemometric analysis. Fi...

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Autores principales: Trawiński, Jakub, Wroński, Michał, Gawlik, Maciej, Skibiński, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8839339/
https://www.ncbi.nlm.nih.gov/pubmed/35164027
http://dx.doi.org/10.3390/molecules27030763
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author Trawiński, Jakub
Wroński, Michał
Gawlik, Maciej
Skibiński, Robert
author_facet Trawiński, Jakub
Wroński, Michał
Gawlik, Maciej
Skibiński, Robert
author_sort Trawiński, Jakub
collection PubMed
description In this study, the phase I hepatic metabolism pathway of a cardiovascular drug nebivolol was proposed on the basis of a human liver microsomes assay with the use of LC-HR-MS coupled with the chemometric method. Six biotransformation products were found with the assistance of chemometric analysis. Five of them were identified as the previously reported products of alicyclic hydroxylation and dihydroxylation, aromatic hydroxylation, as well as alicyclic oxidation of the parent compound. Moreover, one metabolite, not reported so far, was found to be a product of N-dealkylation of nebivolol—2-amino-1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethan-1-ol. The novel metabolite was submitted to an in silico toxicity analysis to assess its biological properties. The applied computational methods indicated a significantly elevated risk of its mutagenic activity, compared to the parent molecule. Several metabolites of the nebivolol described in the literature were not detected in this study, indicating their non-hepatic origin.
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spelling pubmed-88393392022-02-13 Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics Trawiński, Jakub Wroński, Michał Gawlik, Maciej Skibiński, Robert Molecules Article In this study, the phase I hepatic metabolism pathway of a cardiovascular drug nebivolol was proposed on the basis of a human liver microsomes assay with the use of LC-HR-MS coupled with the chemometric method. Six biotransformation products were found with the assistance of chemometric analysis. Five of them were identified as the previously reported products of alicyclic hydroxylation and dihydroxylation, aromatic hydroxylation, as well as alicyclic oxidation of the parent compound. Moreover, one metabolite, not reported so far, was found to be a product of N-dealkylation of nebivolol—2-amino-1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)ethan-1-ol. The novel metabolite was submitted to an in silico toxicity analysis to assess its biological properties. The applied computational methods indicated a significantly elevated risk of its mutagenic activity, compared to the parent molecule. Several metabolites of the nebivolol described in the literature were not detected in this study, indicating their non-hepatic origin. MDPI 2022-01-24 /pmc/articles/PMC8839339/ /pubmed/35164027 http://dx.doi.org/10.3390/molecules27030763 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Trawiński, Jakub
Wroński, Michał
Gawlik, Maciej
Skibiński, Robert
Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics
title Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics
title_full Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics
title_fullStr Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics
title_full_unstemmed Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics
title_short Identification of the New Metabolite of Nebivolol Using Liquid Chromatography Coupled with High-Resolution Mass Spectrometry and Chemometrics
title_sort identification of the new metabolite of nebivolol using liquid chromatography coupled with high-resolution mass spectrometry and chemometrics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8839339/
https://www.ncbi.nlm.nih.gov/pubmed/35164027
http://dx.doi.org/10.3390/molecules27030763
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