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Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode

Understanding the metabolism of pharmaceutical compounds is a fundamental prerequisite for ensuring their safety and efficacy in clinical use. However, conventional methods for monitoring drug metabolism often come with the drawbacks of being time-consuming and costly. In an ongoing quest for innova...

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Autores principales: Wroński, Michał, Trawiński, Jakub, Skibiński, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674253/
https://www.ncbi.nlm.nih.gov/pubmed/38004565
http://dx.doi.org/10.3390/pharmaceutics15112586
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author Wroński, Michał
Trawiński, Jakub
Skibiński, Robert
author_facet Wroński, Michał
Trawiński, Jakub
Skibiński, Robert
author_sort Wroński, Michał
collection PubMed
description Understanding the metabolism of pharmaceutical compounds is a fundamental prerequisite for ensuring their safety and efficacy in clinical use. However, conventional methods for monitoring drug metabolism often come with the drawbacks of being time-consuming and costly. In an ongoing quest for innovative approaches, the application of electrochemistry in metabolism studies has gained prominence as a promising approach for the synthesis and analysis of drug transformation products. In this study, we investigated the hepatic metabolism of voriconazole, an antifungal medication, by utilizing human liver microsomes (HLM) assay coupled with LC-MS. Based on the obtained results, the electrochemical parameters were optimized to simulate the biotransformation reactions. Among the various electrodes tested, the chemometric analysis revealed that the iron(II) phthalocyanine electrode was the most effective in catalyzing the formation of all hepatic voriconazole metabolites. These findings exemplify the potential of phthalocyanine electrodes as an efficient and cost-effective tool for simulating the intricate metabolic processes involved in drug biotransformation, offering new possibilities in the field of pharmaceutical research. Additionally, in silico analysis showed that two detected metabolites may exhibit significantly higher acute toxicity and mutagenic potential than the parent compound.
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spelling pubmed-106742532023-11-04 Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode Wroński, Michał Trawiński, Jakub Skibiński, Robert Pharmaceutics Article Understanding the metabolism of pharmaceutical compounds is a fundamental prerequisite for ensuring their safety and efficacy in clinical use. However, conventional methods for monitoring drug metabolism often come with the drawbacks of being time-consuming and costly. In an ongoing quest for innovative approaches, the application of electrochemistry in metabolism studies has gained prominence as a promising approach for the synthesis and analysis of drug transformation products. In this study, we investigated the hepatic metabolism of voriconazole, an antifungal medication, by utilizing human liver microsomes (HLM) assay coupled with LC-MS. Based on the obtained results, the electrochemical parameters were optimized to simulate the biotransformation reactions. Among the various electrodes tested, the chemometric analysis revealed that the iron(II) phthalocyanine electrode was the most effective in catalyzing the formation of all hepatic voriconazole metabolites. These findings exemplify the potential of phthalocyanine electrodes as an efficient and cost-effective tool for simulating the intricate metabolic processes involved in drug biotransformation, offering new possibilities in the field of pharmaceutical research. Additionally, in silico analysis showed that two detected metabolites may exhibit significantly higher acute toxicity and mutagenic potential than the parent compound. MDPI 2023-11-04 /pmc/articles/PMC10674253/ /pubmed/38004565 http://dx.doi.org/10.3390/pharmaceutics15112586 Text en © 2023 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
Wroński, Michał
Trawiński, Jakub
Skibiński, Robert
Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode
title Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode
title_full Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode
title_fullStr Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode
title_full_unstemmed Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode
title_short Electrochemical Simulation of Phase I Hepatic Metabolism of Voriconazole Using a Screen-Printed Iron(II) Phthalocyanine Electrode
title_sort electrochemical simulation of phase i hepatic metabolism of voriconazole using a screen-printed iron(ii) phthalocyanine electrode
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674253/
https://www.ncbi.nlm.nih.gov/pubmed/38004565
http://dx.doi.org/10.3390/pharmaceutics15112586
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