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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Journal of the Brazilian Chemical Society; v. 30, n. 7, p. 1415-1424, JUL 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/14150-8 - Funcionalização seletiva de aromáticos: estudos metodológicos e novas aplicações na síntese de substâncias bioativas
• Beneficiário: Giuliano Cesar Clososki
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/12811-9 - Funcionalização dirigida de arenos e heteroarenos visando a síntese de substâncias de interesse medicinal
• Beneficiário: Giuliano Cesar Clososki
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/50265-3 - Metabolismo e distribuição de xenobióticos naturais e sintéticos: da compreensão dos processos reacionais à geração de imagens teciduais
• Beneficiário: Norberto Peporine Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Temático