Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach

Autores
Bedogni, Giselle Rocio; Azcarate, Federcio José; Seremeta, Katia Pamela; Okulik, Nora Beatriz; Salomon, Claudio Javier; Boschetti, Carlos Eugenio
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The study depicts the successful development and validation of a simple and fast reverse-phase high-performance liquid chromatography (RP-HPLC) method for the separation of nifurtimox (NFX) and its degradation products. NFX was exposed to different degradation conditions and a RP-HPLC method reported in the literature was used to evaluate different peaks that could interfere with the one from the pure NFX. NaOH generated a degradation product, with a peak that tends to overlap with NFX. Therefore, the NFX exposed to this condition was used during screening and optimization of the RP-HPLC method using a Design of Experiment (DoE) approach. A factorial design was applied to screen different factors, followed by a central composite design for process optimization with those factors that significantly affected the evaluated responses during the screening step. The optimized method was further validated according to International Conference of Harmonization guidelines. Methanol proportion and gradient time to reach it, alongside with mobile phase flow rate, were the factors that had a statistically significant effect on resolution, retention time, and tailing factor in the chromatographic peak. The optimized chromatographic parameters were: 41.6 % of methanol, a gradient time of 2 min, and a flow rate of 0.62 mL/min. Under these chromatographic conditions, the retention time of NFX was 5.3 min, while for the nearest degradation products was 4.5 min and 6.3 min. The resolution of the NFX peak was 5.14 and the tailing was 1.13. The DoE approach allowed the development of an optimized RP-HPLC method capable of successfully separating NFX and its forced degradation products.
Fil: Bedogni, Giselle Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Azcarate, Federcio José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; Argentina
Fil: Seremeta, Katia Pamela. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Nordeste. Instituto de Investigaciones En Procesos Tecnologicos Avanzados. - Universidad Nacional del Chaco Austral. Instituto de Investigaciones En Procesos Tecnologicos Avanzados.; Argentina
Fil: Okulik, Nora Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Nordeste. Instituto de Investigaciones En Procesos Tecnologicos Avanzados. - Universidad Nacional del Chaco Austral. Instituto de Investigaciones En Procesos Tecnologicos Avanzados.; Argentina
Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; Argentina
Fil: Boschetti, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; Argentina
Materia
Design of Experiments
Method development
Nifurtimox
HPLC
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/267065
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/267065
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approachBedogni, Giselle RocioAzcarate, Federcio JoséSeremeta, Katia PamelaOkulik, Nora BeatrizSalomon, Claudio JavierBoschetti, Carlos EugenioDesign of ExperimentsMethod developmentNifurtimoxHPLChttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The study depicts the successful development and validation of a simple and fast reverse-phase high-performance liquid chromatography (RP-HPLC) method for the separation of nifurtimox (NFX) and its degradation products. NFX was exposed to different degradation conditions and a RP-HPLC method reported in the literature was used to evaluate different peaks that could interfere with the one from the pure NFX. NaOH generated a degradation product, with a peak that tends to overlap with NFX. Therefore, the NFX exposed to this condition was used during screening and optimization of the RP-HPLC method using a Design of Experiment (DoE) approach. A factorial design was applied to screen different factors, followed by a central composite design for process optimization with those factors that significantly affected the evaluated responses during the screening step. The optimized method was further validated according to International Conference of Harmonization guidelines. Methanol proportion and gradient time to reach it, alongside with mobile phase flow rate, were the factors that had a statistically significant effect on resolution, retention time, and tailing factor in the chromatographic peak. The optimized chromatographic parameters were: 41.6 % of methanol, a gradient time of 2 min, and a flow rate of 0.62 mL/min. Under these chromatographic conditions, the retention time of NFX was 5.3 min, while for the nearest degradation products was 4.5 min and 6.3 min. The resolution of the NFX peak was 5.14 and the tailing was 1.13. The DoE approach allowed the development of an optimized RP-HPLC method capable of successfully separating NFX and its forced degradation products.Fil: Bedogni, Giselle Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Azcarate, Federcio José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; ArgentinaFil: Seremeta, Katia Pamela. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Nordeste. Instituto de Investigaciones En Procesos Tecnologicos Avanzados. - Universidad Nacional del Chaco Austral. Instituto de Investigaciones En Procesos Tecnologicos Avanzados.; ArgentinaFil: Okulik, Nora Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Nordeste. Instituto de Investigaciones En Procesos Tecnologicos Avanzados. - Universidad Nacional del Chaco Austral. Instituto de Investigaciones En Procesos Tecnologicos Avanzados.; ArgentinaFil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; ArgentinaFil: Boschetti, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; ArgentinaElsevier Science2024-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/267065Bedogni, Giselle Rocio; Azcarate, Federcio José; Seremeta, Katia Pamela; Okulik, Nora Beatriz; Salomon, Claudio Javier; et al.; Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach; Elsevier Science; Journal of Molecular Liquids; 399; 124293; 4-2024; 1-230167-7322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0167732224003490info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molliq.2024.124293info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T15:50:56Zoai:ri.conicet.gov.ar:11336/267065instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 15:50:56.426CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach
title Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach
spellingShingle Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach
Bedogni, Giselle Rocio
Design of Experiments
Method development
Nifurtimox
HPLC
title_short Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach
title_full Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach
title_fullStr Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach
title_full_unstemmed Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach
title_sort Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach
dc.creator.none.fl_str_mv Bedogni, Giselle Rocio
Azcarate, Federcio José
Seremeta, Katia Pamela
Okulik, Nora Beatriz
Salomon, Claudio Javier
Boschetti, Carlos Eugenio
author Bedogni, Giselle Rocio
author_facet Bedogni, Giselle Rocio
Azcarate, Federcio José
Seremeta, Katia Pamela
Okulik, Nora Beatriz
Salomon, Claudio Javier
Boschetti, Carlos Eugenio
author_role author
author2 Azcarate, Federcio José
Seremeta, Katia Pamela
Okulik, Nora Beatriz
Salomon, Claudio Javier
Boschetti, Carlos Eugenio
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Design of Experiments
Method development
Nifurtimox
HPLC
topic Design of Experiments
Method development
Nifurtimox
HPLC
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The study depicts the successful development and validation of a simple and fast reverse-phase high-performance liquid chromatography (RP-HPLC) method for the separation of nifurtimox (NFX) and its degradation products. NFX was exposed to different degradation conditions and a RP-HPLC method reported in the literature was used to evaluate different peaks that could interfere with the one from the pure NFX. NaOH generated a degradation product, with a peak that tends to overlap with NFX. Therefore, the NFX exposed to this condition was used during screening and optimization of the RP-HPLC method using a Design of Experiment (DoE) approach. A factorial design was applied to screen different factors, followed by a central composite design for process optimization with those factors that significantly affected the evaluated responses during the screening step. The optimized method was further validated according to International Conference of Harmonization guidelines. Methanol proportion and gradient time to reach it, alongside with mobile phase flow rate, were the factors that had a statistically significant effect on resolution, retention time, and tailing factor in the chromatographic peak. The optimized chromatographic parameters were: 41.6 % of methanol, a gradient time of 2 min, and a flow rate of 0.62 mL/min. Under these chromatographic conditions, the retention time of NFX was 5.3 min, while for the nearest degradation products was 4.5 min and 6.3 min. The resolution of the NFX peak was 5.14 and the tailing was 1.13. The DoE approach allowed the development of an optimized RP-HPLC method capable of successfully separating NFX and its forced degradation products.
Fil: Bedogni, Giselle Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Azcarate, Federcio José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; Argentina
Fil: Seremeta, Katia Pamela. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Nordeste. Instituto de Investigaciones En Procesos Tecnologicos Avanzados. - Universidad Nacional del Chaco Austral. Instituto de Investigaciones En Procesos Tecnologicos Avanzados.; Argentina
Fil: Okulik, Nora Beatriz. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Nordeste. Instituto de Investigaciones En Procesos Tecnologicos Avanzados. - Universidad Nacional del Chaco Austral. Instituto de Investigaciones En Procesos Tecnologicos Avanzados.; Argentina
Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; Argentina
Fil: Boschetti, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Procesos Biotecnológicos y Químicos Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Procesos Biotecnológicos y Químicos Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas.; Argentina
description The study depicts the successful development and validation of a simple and fast reverse-phase high-performance liquid chromatography (RP-HPLC) method for the separation of nifurtimox (NFX) and its degradation products. NFX was exposed to different degradation conditions and a RP-HPLC method reported in the literature was used to evaluate different peaks that could interfere with the one from the pure NFX. NaOH generated a degradation product, with a peak that tends to overlap with NFX. Therefore, the NFX exposed to this condition was used during screening and optimization of the RP-HPLC method using a Design of Experiment (DoE) approach. A factorial design was applied to screen different factors, followed by a central composite design for process optimization with those factors that significantly affected the evaluated responses during the screening step. The optimized method was further validated according to International Conference of Harmonization guidelines. Methanol proportion and gradient time to reach it, alongside with mobile phase flow rate, were the factors that had a statistically significant effect on resolution, retention time, and tailing factor in the chromatographic peak. The optimized chromatographic parameters were: 41.6 % of methanol, a gradient time of 2 min, and a flow rate of 0.62 mL/min. Under these chromatographic conditions, the retention time of NFX was 5.3 min, while for the nearest degradation products was 4.5 min and 6.3 min. The resolution of the NFX peak was 5.14 and the tailing was 1.13. The DoE approach allowed the development of an optimized RP-HPLC method capable of successfully separating NFX and its forced degradation products.
publishDate 2024
dc.date.none.fl_str_mv 2024-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/267065
Bedogni, Giselle Rocio; Azcarate, Federcio José; Seremeta, Katia Pamela; Okulik, Nora Beatriz; Salomon, Claudio Javier; et al.; Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach; Elsevier Science; Journal of Molecular Liquids; 399; 124293; 4-2024; 1-23
0167-7322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/267065
identifier_str_mv Bedogni, Giselle Rocio; Azcarate, Federcio José; Seremeta, Katia Pamela; Okulik, Nora Beatriz; Salomon, Claudio Javier; et al.; Development of a fast RP-HPLC method for the separation of nifurtimox and its forced degradation products through a design of experiment approach; Elsevier Science; Journal of Molecular Liquids; 399; 124293; 4-2024; 1-23
0167-7322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0167732224003490
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molliq.2024.124293
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.265058

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