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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity

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de Mello, Murilo B. M. [1] ; de Oliveira, Antonio A. F. [2] ; de Oliveira, Caroline L. [2] ; Ultramari, Mariah A. [2] ; Gaeta, Fernando H. S. [2] ; Mascarello, Alessandra [2] ; Guimaraes, Cristiano R. W. [2] ; de Freitas, Miller N. [2] ; Cunha, Carlos E. [3] ; Lourenco, Tiago C. [4] ; Ferreira, Fernandez P. [5] ; Lopes, Joao L. C. [1, 6] ; Clososki, Giuliano C. [1]
Total Authors: 13
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, NPPNS, Av Cafe S-N, BR-14040903 Ribeirao Preto - Brazil
[2] Ache Labs Farmaceut SA, Rodovia Presidente Dutra, Km 222, 2, BR-07034904 Guarulhos, SP - Brazil
[3] Lhasa Ltd, Granary Wharf House, 2 Canal Wharf, Leeds LS11 5PS, W Yorkshire - England
[4] Apex Sci, Ave Marechal Rondon 2148, BR-13070173 Campinas, SP - Brazil
[5] Lychnoflora Pesquisa & Desenvolvimento Prod Nat, Rua Angelo Mestriner 263, BR-14030090 Ribeirao Preto - Brazil
[6] Avita Prod Quim & Farmaceut, Av Dra Nadir Aguiar 1805, Mod 27 B, BR-14056680 Ribeirao Preto - Brazil
Total Affiliations: 6
Document type: Journal article
Source: Journal of the Brazilian Chemical Society; v. 30, n. 7, p. 1415-1424, JUL 2019.
Web of Science Citations: 0

Currently, the pharmaceutical industry devotes great attention to drug degradation products because these compounds can offer risks to patients. A previous degradation study of betahistine (N-α-methyl-2-pyridylethylamine) conducted under different stress conditions detected three main impurities named A, B and C. Degradation products were analyzed by high-resolution mass spectrometry in electrospray source and time of flight analyzer (ESI-TOF) and nuclear magnetic resonance (NMR). Impurity mutagenicity was evaluated by Derek Nexus and Sarah Nexus softwares. Liquid chromatography hyphenate with tandem mass spectrometry (LC-MS/MS) analysis of the betahistine forced degradation sample indicated the presence of a new impurity, which was named impurity C1. 2D NMR experiments allowed the complete structural characterization of the new entity. The active pharmaceutical ingredient and degradation impurities were classified as inactive in the in silico mutagenic studies. Systematic investigation of a forced degradation sample led to the characterization of a new betahistine impurity. The in silico mutagenicity study of the betahistine degradation impurities may be useful in the risk assessment of the drug products. (AU)

FAPESP's process: 18/14150-8 - Selective aromatic functionalization: Methodological Studies and new applications in the synthesis of BIOATIVE compounds
Grantee:Giuliano Cesar Clososki
Support Opportunities: Regular Research Grants
Grantee:Giuliano Cesar Clososki
Support Opportunities: Regular Research Grants
FAPESP's process: 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation
Grantee:Norberto Peporine Lopes
Support Opportunities: BIOTA-FAPESP Program - Thematic Grants