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Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry

Betulinic acid (BA) has been extensively studied in recent years mainly for its antiproliferative and antitumor effect in various types of cancers. Limited data are available regarding the pharmacokinetic profile of BA, particularly its metabolic transformation in vivo. In this study, we present the...

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Autores principales: Ghiulai, Roxana, Mioc, Marius, Racoviceanu, Roxana, Prodea, Alexandra, Milan, Andreea, Coricovac, Dorina, Dehelean, Cristina, Avram, Ştefana, Zamfir, Alina D., Munteanu, Cristian V. A., Ivan, Viviana, Şoica, Codruța
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656950/
https://www.ncbi.nlm.nih.gov/pubmed/36364186
http://dx.doi.org/10.3390/molecules27217359
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author Ghiulai, Roxana
Mioc, Marius
Racoviceanu, Roxana
Prodea, Alexandra
Milan, Andreea
Coricovac, Dorina
Dehelean, Cristina
Avram, Ştefana
Zamfir, Alina D.
Munteanu, Cristian V. A.
Ivan, Viviana
Şoica, Codruța
author_facet Ghiulai, Roxana
Mioc, Marius
Racoviceanu, Roxana
Prodea, Alexandra
Milan, Andreea
Coricovac, Dorina
Dehelean, Cristina
Avram, Ştefana
Zamfir, Alina D.
Munteanu, Cristian V. A.
Ivan, Viviana
Şoica, Codruța
author_sort Ghiulai, Roxana
collection PubMed
description Betulinic acid (BA) has been extensively studied in recent years mainly for its antiproliferative and antitumor effect in various types of cancers. Limited data are available regarding the pharmacokinetic profile of BA, particularly its metabolic transformation in vivo. In this study, we present the screening and structural investigations by ESI Orbitrap MS in the negative ion mode and CID MS/MS of phase I and phase II metabolites detected in mouse plasma after the intraperitoneal administration of a nanoemulsion containing BA in SKH 1 female mice. Obtained results indicate that the main phase I metabolic reactions that BA undergoes are monohydroxylation, dihydroxylation, oxidation and hydrogenation, while phase II reactions involved sulfation, glucuronidation and methylation. The fragmentation pathway for BA and its plasma metabolites were elucidated by sequencing of the precursor ions by CID MS MS experiments.
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spelling pubmed-96569502022-11-15 Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry Ghiulai, Roxana Mioc, Marius Racoviceanu, Roxana Prodea, Alexandra Milan, Andreea Coricovac, Dorina Dehelean, Cristina Avram, Ştefana Zamfir, Alina D. Munteanu, Cristian V. A. Ivan, Viviana Şoica, Codruța Molecules Article Betulinic acid (BA) has been extensively studied in recent years mainly for its antiproliferative and antitumor effect in various types of cancers. Limited data are available regarding the pharmacokinetic profile of BA, particularly its metabolic transformation in vivo. In this study, we present the screening and structural investigations by ESI Orbitrap MS in the negative ion mode and CID MS/MS of phase I and phase II metabolites detected in mouse plasma after the intraperitoneal administration of a nanoemulsion containing BA in SKH 1 female mice. Obtained results indicate that the main phase I metabolic reactions that BA undergoes are monohydroxylation, dihydroxylation, oxidation and hydrogenation, while phase II reactions involved sulfation, glucuronidation and methylation. The fragmentation pathway for BA and its plasma metabolites were elucidated by sequencing of the precursor ions by CID MS MS experiments. MDPI 2022-10-29 /pmc/articles/PMC9656950/ /pubmed/36364186 http://dx.doi.org/10.3390/molecules27217359 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
Ghiulai, Roxana
Mioc, Marius
Racoviceanu, Roxana
Prodea, Alexandra
Milan, Andreea
Coricovac, Dorina
Dehelean, Cristina
Avram, Ştefana
Zamfir, Alina D.
Munteanu, Cristian V. A.
Ivan, Viviana
Şoica, Codruța
Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry
title Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry
title_full Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry
title_fullStr Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry
title_full_unstemmed Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry
title_short Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry
title_sort structural investigation of betulinic acid plasma metabolites by tandem mass spectrometry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656950/
https://www.ncbi.nlm.nih.gov/pubmed/36364186
http://dx.doi.org/10.3390/molecules27217359
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