Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS

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dc.contributor.authorSversut, Rúbia Adrieli [UNESP]
dc.contributor.authorVieira, James Cabral
dc.contributor.authorKassab, Nájla Mohamad
dc.contributor.authorSilva, Denise Brentan
dc.contributor.authorSalgado, Hérida Regina Nunes [UNESP]
dc.contributor.institutionUniversidade Federal de Mato Grosso do Sul (UFMS)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2019-10-06T17:15:45Z
dc.date.available2019-10-06T17:15:45Z
dc.date.issued2019-11-01
dc.description.abstractOxytetracycline (OTC) belongs to the antimicrobial class, diclofenac sodium (DICLO) and piroxicam (PIRO) are nonsteroidal anti-inflammatory drugs. Fixed-dose combinations of OTC with DICLO or PIRO, available as extended release injectable solutions, are widely indicated for animal use. These drugs were subject to forced degradation (alkaline, acid, neutral, oxidative photolytic conditions) as per ICH Q1 (R2) guideline and the kinetic of degradation reactions was investigated. OTC showed higher degradation under neutral, oxidative, alkaline and acid conditions and DICLO showed extensive photo degradation, while PIRO was the most stable drug under all degradation conditions studied. A total of seven degradation products (DPs) were observed and efficient chromatographic separations of drugs and their DPs were achieved on an InertSustain C8 column using a mobile phase composed by methanol-acetonitrile-water (40:35:25, v/v/v) at pH 2.5, adjusted with formic acid, in isocratic mode. Six DPs were isolated by HPLC-PDA and their chemical structures were proposed based on high resolution MS and MS/MS data. DP 1 to DP 5 had OTC as precursor drug, while DP 6 originated from DICLO photolysis. The chemical structures of DP 1, DP 4 and DP 5 are being reported here for the first time. The HPLC-PDA was adequately validated and it can be used in the quality control routine analysis as stability indicating method for quantification of drugs in pharmaceuticals and evaluation of their accelerated and long-term stability.en
dc.description.affiliationUniversidade Federal de Mato Grosso do Sul (UFMS) Faculdade de Ciências Farmacêuticas Alimentos e Nutrição (FACFAN) Laboratório de Tecnologia Farmacêutica (LTF)
dc.description.affiliationUniversidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas
dc.description.affiliationUniversidade Federal de Mato Grosso do Sul (UFMS) Faculdade de Ciências Farmacêuticas Alimentos e Nutrição (FACFAN) Laboratório de Produtos Naturais e Espectrometria de Massas (LaPNEM)
dc.description.affiliationUnespUniversidade Estadual Paulista (UNESP) Faculdade de Ciências Farmacêuticas
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.identifierhttp://dx.doi.org/10.1016/j.microc.2019.104074
dc.identifier.citationMicrochemical Journal, v. 150.
dc.identifier.doi10.1016/j.microc.2019.104074
dc.identifier.issn0026-265X
dc.identifier.scopus2-s2.0-85069636544
dc.identifier.urihttp://hdl.handle.net/11449/190517
dc.language.isoeng
dc.relation.ispartofMicrochemical Journal
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectForced degradation studies
dc.subjectKinetic models
dc.subjectOxytetracycline
dc.subjectPiroxicam
dc.subjectSodium diclofenac
dc.subjectStability indicating method
dc.titleForced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MSen
dc.typeArtigo

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