Structural Investigation of Betulinic Acid Plasma Metabolites by Tandem Mass Spectrometry
Roxana Ghiulai,
Marius Mioc,
Roxana Racoviceanu,
Alexandra Prodea,
Andreea Milan,
Dorina Coricovac,
Cristina Dehelean,
Ștefana Avram,
Alina D. Zamfir,
Cristian V. A. Munteanu,
Viviana Ivan,
Codruța Şoica
Affiliations
Roxana Ghiulai
Department of Pharmacology-Pharmacotherapy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
Marius Mioc
Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
Roxana Racoviceanu
Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
Alexandra Prodea
Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
Andreea Milan
Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
Dorina Coricovac
Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
Cristina Dehelean
Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
Ștefana Avram
Research Centre for Pharmaco-Toxicological Evaluation, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
Alina D. Zamfir
Department of Condensed Matter, National Institute for Research and Development in Electrochemistry and Condensed Matter, 300224 Timisoara, Romania
Cristian V. A. Munteanu
Institute of Biochemistry of the Romanian Academy, Splaiul Independent, ei 296, 060031 Bucharest, Romania
Viviana Ivan
Department of Internal Medicine II, Faculty of Medicine, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu S.2, 300041 Timisoara, Romania
Codruța Şoica
Department of Pharmacology-Pharmacotherapy, Victor Babes University of Medicine and Pharmacy Timisoara, 2nd Eftimie Murgu Sq., 300041 Timisoara, Romania
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.
