Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/103829 https://doi.org/10.3390/chemosensors9070172 |
Resumo: | An Analytical Quality by Design (AQbD) approach is presented, aiming at the development and validation of an HPLC method for the quantification of disulfiram and copper diethyldithiocarbamate in lipid nanoparticles. Following the definition of the analytical target profile (ATP), encompassing the critical analytical attributes (CAA), a two-level risk assessment strategy (Ishikawa diagram—failure mode and effect analysis (FMEA)) was employed to identify the critical method parameters (CMPs) with an extensive impact on method performance. The behavior of the CMPs (flow rate and mobile phase composition) was further characterized by experimental design, resorting to a face-centered central composite design (FcCCD). Statistical modeling, response surface analysis, and Monte Carlo simulations led to the definition of the Method Operable Design Region (MODR), associated with a negligible risk of failing the predefined CAA specifications. The optimal method was validated according to international regulatory recommendations. Apart from guaranteeing linearity, accuracy, precision, specificity, robustness, and stability, these conditions were found to be suitable for analysis using a different HPLC column and equipment. In a nutshell, the development and optimization strategies, under the comprehensive framework of AQbD, provided an effective, simple, rapid, reliable, and flexible method for routine analysis of the compounds in research or industrial environments. |
id |
RCAP_a356354abfea870497e31635267af097 |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/103829 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design ApproachAQbDcancercentral composite designcopper diethyldithiocarbamatedisulfiramlipid nanoparticlesliquid chromatographymethod optimizationmethod robustnessMODRAn Analytical Quality by Design (AQbD) approach is presented, aiming at the development and validation of an HPLC method for the quantification of disulfiram and copper diethyldithiocarbamate in lipid nanoparticles. Following the definition of the analytical target profile (ATP), encompassing the critical analytical attributes (CAA), a two-level risk assessment strategy (Ishikawa diagram—failure mode and effect analysis (FMEA)) was employed to identify the critical method parameters (CMPs) with an extensive impact on method performance. The behavior of the CMPs (flow rate and mobile phase composition) was further characterized by experimental design, resorting to a face-centered central composite design (FcCCD). Statistical modeling, response surface analysis, and Monte Carlo simulations led to the definition of the Method Operable Design Region (MODR), associated with a negligible risk of failing the predefined CAA specifications. The optimal method was validated according to international regulatory recommendations. Apart from guaranteeing linearity, accuracy, precision, specificity, robustness, and stability, these conditions were found to be suitable for analysis using a different HPLC column and equipment. In a nutshell, the development and optimization strategies, under the comprehensive framework of AQbD, provided an effective, simple, rapid, reliable, and flexible method for routine analysis of the compounds in research or industrial environments.MDPI2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/103829http://hdl.handle.net/10316/103829https://doi.org/10.3390/chemosensors9070172eng2227-9040Basso, JoãoRamos, Maria LuísaPais, AlbertoVitorino, RuiFortuna, AnaVitorino, Carlainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-11-30T21:38:26Zoai:estudogeral.uc.pt:10316/103829Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:20:36.034525Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach |
title |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach |
spellingShingle |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach Basso, João AQbD cancer central composite design copper diethyldithiocarbamate disulfiram lipid nanoparticles liquid chromatography method optimization method robustness MODR |
title_short |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach |
title_full |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach |
title_fullStr |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach |
title_full_unstemmed |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach |
title_sort |
Expediting Disulfiram Assays through a Systematic Analytical Quality by Design Approach |
author |
Basso, João |
author_facet |
Basso, João Ramos, Maria Luísa Pais, Alberto Vitorino, Rui Fortuna, Ana Vitorino, Carla |
author_role |
author |
author2 |
Ramos, Maria Luísa Pais, Alberto Vitorino, Rui Fortuna, Ana Vitorino, Carla |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Basso, João Ramos, Maria Luísa Pais, Alberto Vitorino, Rui Fortuna, Ana Vitorino, Carla |
dc.subject.por.fl_str_mv |
AQbD cancer central composite design copper diethyldithiocarbamate disulfiram lipid nanoparticles liquid chromatography method optimization method robustness MODR |
topic |
AQbD cancer central composite design copper diethyldithiocarbamate disulfiram lipid nanoparticles liquid chromatography method optimization method robustness MODR |
description |
An Analytical Quality by Design (AQbD) approach is presented, aiming at the development and validation of an HPLC method for the quantification of disulfiram and copper diethyldithiocarbamate in lipid nanoparticles. Following the definition of the analytical target profile (ATP), encompassing the critical analytical attributes (CAA), a two-level risk assessment strategy (Ishikawa diagram—failure mode and effect analysis (FMEA)) was employed to identify the critical method parameters (CMPs) with an extensive impact on method performance. The behavior of the CMPs (flow rate and mobile phase composition) was further characterized by experimental design, resorting to a face-centered central composite design (FcCCD). Statistical modeling, response surface analysis, and Monte Carlo simulations led to the definition of the Method Operable Design Region (MODR), associated with a negligible risk of failing the predefined CAA specifications. The optimal method was validated according to international regulatory recommendations. Apart from guaranteeing linearity, accuracy, precision, specificity, robustness, and stability, these conditions were found to be suitable for analysis using a different HPLC column and equipment. In a nutshell, the development and optimization strategies, under the comprehensive framework of AQbD, provided an effective, simple, rapid, reliable, and flexible method for routine analysis of the compounds in research or industrial environments. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 |
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://hdl.handle.net/10316/103829 http://hdl.handle.net/10316/103829 https://doi.org/10.3390/chemosensors9070172 |
url |
http://hdl.handle.net/10316/103829 https://doi.org/10.3390/chemosensors9070172 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2227-9040 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799134098375049216 |