Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.microc.2019.104074 http://hdl.handle.net/11449/190517 |
Resumo: | Oxytetracycline (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. |
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Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MSForced degradation studiesKinetic modelsOxytetracyclinePiroxicamSodium diclofenacStability indicating methodOxytetracycline (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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de Mato Grosso do Sul (UFMS) Faculdade de Ciências Farmacêuticas Alimentos e Nutrição (FACFAN) Laboratório de Tecnologia Farmacêutica (LTF)Universidade Estadual Paulista (UNESP) Faculdade de Ciências FarmacêuticasUniversidade Federal de Mato Grosso do Sul (UFMS) Faculdade de Ciências Farmacêuticas Alimentos e Nutrição (FACFAN) Laboratório de Produtos Naturais e Espectrometria de Massas (LaPNEM)Universidade Estadual Paulista (UNESP) Faculdade de Ciências FarmacêuticasUniversidade Federal de Mato Grosso do Sul (UFMS)Universidade Estadual Paulista (Unesp)Sversut, Rúbia Adrieli [UNESP]Vieira, James CabralKassab, Nájla MohamadSilva, Denise BrentanSalgado, Hérida Regina Nunes [UNESP]2019-10-06T17:15:45Z2019-10-06T17:15:45Z2019-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.microc.2019.104074Microchemical Journal, v. 150.0026-265Xhttp://hdl.handle.net/11449/19051710.1016/j.microc.2019.1040742-s2.0-85069636544Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMicrochemical Journalinfo:eu-repo/semantics/openAccess2024-06-24T13:46:11Zoai:repositorio.unesp.br:11449/190517Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:42:29.942890Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS |
title |
Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS |
spellingShingle |
Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS Sversut, Rúbia Adrieli [UNESP] Forced degradation studies Kinetic models Oxytetracycline Piroxicam Sodium diclofenac Stability indicating method |
title_short |
Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS |
title_full |
Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS |
title_fullStr |
Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS |
title_full_unstemmed |
Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS |
title_sort |
Forced degradation behavior of two-drug combinations: Isolation and characterization of major degradation products by LC-MS |
author |
Sversut, Rúbia Adrieli [UNESP] |
author_facet |
Sversut, Rúbia Adrieli [UNESP] Vieira, James Cabral Kassab, Nájla Mohamad Silva, Denise Brentan Salgado, Hérida Regina Nunes [UNESP] |
author_role |
author |
author2 |
Vieira, James Cabral Kassab, Nájla Mohamad Silva, Denise Brentan Salgado, Hérida Regina Nunes [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Mato Grosso do Sul (UFMS) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Sversut, Rúbia Adrieli [UNESP] Vieira, James Cabral Kassab, Nájla Mohamad Silva, Denise Brentan Salgado, Hérida Regina Nunes [UNESP] |
dc.subject.por.fl_str_mv |
Forced degradation studies Kinetic models Oxytetracycline Piroxicam Sodium diclofenac Stability indicating method |
topic |
Forced degradation studies Kinetic models Oxytetracycline Piroxicam Sodium diclofenac Stability indicating method |
description |
Oxytetracycline (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. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T17:15:45Z 2019-10-06T17:15:45Z 2019-11-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.microc.2019.104074 Microchemical Journal, v. 150. 0026-265X http://hdl.handle.net/11449/190517 10.1016/j.microc.2019.104074 2-s2.0-85069636544 |
url |
http://dx.doi.org/10.1016/j.microc.2019.104074 http://hdl.handle.net/11449/190517 |
identifier_str_mv |
Microchemical Journal, v. 150. 0026-265X 10.1016/j.microc.2019.104074 2-s2.0-85069636544 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Microchemical Journal |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129238189998080 |