Stability-indicating methods applied in the separation and characterization of the main degradation product of propafenone

Autor(es)

de Almeida Leite, Heitor Oliveira ^[1] ; Kassab, Najla Mohamad ^[2] ; Aurora Prado, Maria Segunda ^[1] ; Singh, Anil Kumar ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Pharm, Av Prof Lineu Prestes 580, Cidade Univ, Sao Paulo, SP - Brazil

^[2] Univ Fed Mato Grosso do Sul, Ctr Biol Sci & Hlth, Grad Program Pharm, Campo Grande, MS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SEPARATION SCIENCE PLUS; v. 1, n. 7, p. 490-497, JUL 2018.
• Citações Web of Science: 0

Resumo

Propafenone hydrochloride is used in the treatment of supraventricular and ventricular arrhythmias and it has sodium channel blocking and beta-blocking activity. To evaluate the quality, safety and efficacy of propafenone drug products, a stability-indicating method must be used, aiming at qualitative and/or quantitative assessment of the impurities and degradation products contained therein. The main purpose of this study was to develop and apply hyphenated high-performance liquid chromatography with diode array detection and liquid chromatography with mass spectrometry methods to access susceptibility of the propafenone hydrochloride to stress conditions. The degradation process and products were systematically evaluated through in silico and predictive mass balance approaches. The main acidic and oxidative degradation product was characterized by using liquid chromatography with mass spectrometry. Propafenone hydrochloride was found to be highly susceptible to oxidative (peroxide) and thermal degradation. However, an alkaline medium has an insignificant impact on the stability of propafenone hydrochloride. A plausible path for the acidic degradation product is described and elucidated. (AU)

• Processo FAPESP: 15/11210-1 - Aplicação de cromotografia líquida de alta eficiência e eletroforese capilar para determinação de perfil de impurezas dos fármacos anti-histamínicos de terceira geração
• Beneficiário: Anil Kumar Singh
• Modalidade de apoio: Auxílio à Pesquisa - Regular