학술논문
Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry.
Document Type
Academic Journal
Author
Ghiulai R; Department of Pharmacology-Pharmacotherapy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Mioc M; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Racoviceanu R; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Prodea A; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Milan A; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Coricovac D; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Department of Toxicology, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Dehelean C; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Department of Toxicology, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Avram Ș; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Department of Pharmacognosy, Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Zamfir AD; Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300224 Timisoara, Romania.; Faculty of Physics, West University of Timisoara, 300223 Timisoara, Romania.; Munteanu CVA; Institute of Biochemistry of the Romanian Academy, Splaiul Independent, ei 296, 060031 Bucharest, Romania.; Ivan V; Department of Internal Medicine II, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu S.2, 300041 Timisoara, Romania.; Şoica C; Department of Pharmacology-Pharmacotherapy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.; Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
Subject
Language
English
Abstract
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.