Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment

Autores
Galindo Bedor, Danilo César; Tavares Cavalcanti Bedor, Noely Camila; Wellithom Viturino da Silva, José; Damasceno Sousa, Giovana; Pereira de Santana, Davi; Garcia Bournissen, Facundo; Altcheh, Jaime Marcelo; Blum, Bethania; Alves, Fabiana; Ribeiro, Isabela
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng · ml1. Intra- and interday precision and bias values were less than 14.87% (n 9) and 9.81% (n 27), respectively. The recovery rates ranged from 94 to 100% with no matrix effect. There was no hematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for more than one year. This article describes the first microsampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and pediatric patients in remote areas and helps to address existing knowledge gaps in the treatment of CD.
Fil: Galindo Bedor, Danilo César. Universidade Federal de Pernambuco; Brasil
Fil: Tavares Cavalcanti Bedor, Noely Camila. No especifíca;
Fil: Wellithom Viturino da Silva, José. Universidade Federal de Pernambuco; Brasil
Fil: Damasceno Sousa, Giovana. Universidade Federal de Pernambuco; Brasil
Fil: Pereira de Santana, Davi. Universidade Federal de Pernambuco; Brasil
Fil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Blum, Bethania. No especifíca;
Fil: Alves, Fabiana. No especifíca;
Fil: Ribeiro, Isabela. No especifíca;
Materia
BENZNIDAZOLE
DRIED BLOOD SPOTS
LC-MS/MS
PHARMACOKINETICS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/130191
Acceder
id CONICETDig_9fe23ed9e73ab805d995360717a95081
oai_identifier_str oai:ri.conicet.gov.ar:11336/130191
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessmentGalindo Bedor, Danilo CésarTavares Cavalcanti Bedor, Noely CamilaWellithom Viturino da Silva, JoséDamasceno Sousa, GiovanaPereira de Santana, DaviGarcia Bournissen, FacundoAltcheh, Jaime MarceloBlum, BethaniaAlves, FabianaRibeiro, IsabelaBENZNIDAZOLEDRIED BLOOD SPOTSLC-MS/MSPHARMACOKINETICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng · ml1. Intra- and interday precision and bias values were less than 14.87% (n 9) and 9.81% (n 27), respectively. The recovery rates ranged from 94 to 100% with no matrix effect. There was no hematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for more than one year. This article describes the first microsampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and pediatric patients in remote areas and helps to address existing knowledge gaps in the treatment of CD.Fil: Galindo Bedor, Danilo César. Universidade Federal de Pernambuco; BrasilFil: Tavares Cavalcanti Bedor, Noely Camila. No especifíca;Fil: Wellithom Viturino da Silva, José. Universidade Federal de Pernambuco; BrasilFil: Damasceno Sousa, Giovana. Universidade Federal de Pernambuco; BrasilFil: Pereira de Santana, Davi. Universidade Federal de Pernambuco; BrasilFil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Blum, Bethania. No especifíca;Fil: Alves, Fabiana. No especifíca;Fil: Ribeiro, Isabela. No especifíca;American Society for Microbiology2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/130191Galindo Bedor, Danilo César ; Tavares Cavalcanti Bedor, Noely Camila ; Wellithom Viturino da Silva, José ; Damasceno Sousa, Giovana ; Pereira de Santana, Davi ; et al.; Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 62; 12; 12-2018; 1-120066-4804CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.00845-18info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:39:28Zoai:ri.conicet.gov.ar:11336/130191instacron: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:34982025-10-15 14:39:28.543CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment
title Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment
spellingShingle Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment
Galindo Bedor, Danilo César
BENZNIDAZOLE
DRIED BLOOD SPOTS
LC-MS/MS
PHARMACOKINETICS
title_short Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment
title_full Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment
title_fullStr Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment
title_full_unstemmed Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment
title_sort Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment
dc.creator.none.fl_str_mv Galindo Bedor, Danilo César
Tavares Cavalcanti Bedor, Noely Camila
Wellithom Viturino da Silva, José
Damasceno Sousa, Giovana
Pereira de Santana, Davi
Garcia Bournissen, Facundo
Altcheh, Jaime Marcelo
Blum, Bethania
Alves, Fabiana
Ribeiro, Isabela
author Galindo Bedor, Danilo César
author_facet Galindo Bedor, Danilo César
Tavares Cavalcanti Bedor, Noely Camila
Wellithom Viturino da Silva, José
Damasceno Sousa, Giovana
Pereira de Santana, Davi
Garcia Bournissen, Facundo
Altcheh, Jaime Marcelo
Blum, Bethania
Alves, Fabiana
Ribeiro, Isabela
author_role author
author2 Tavares Cavalcanti Bedor, Noely Camila
Wellithom Viturino da Silva, José
Damasceno Sousa, Giovana
Pereira de Santana, Davi
Garcia Bournissen, Facundo
Altcheh, Jaime Marcelo
Blum, Bethania
Alves, Fabiana
Ribeiro, Isabela
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BENZNIDAZOLE
DRIED BLOOD SPOTS
LC-MS/MS
PHARMACOKINETICS
topic BENZNIDAZOLE
DRIED BLOOD SPOTS
LC-MS/MS
PHARMACOKINETICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng · ml1. Intra- and interday precision and bias values were less than 14.87% (n 9) and 9.81% (n 27), respectively. The recovery rates ranged from 94 to 100% with no matrix effect. There was no hematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for more than one year. This article describes the first microsampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and pediatric patients in remote areas and helps to address existing knowledge gaps in the treatment of CD.
Fil: Galindo Bedor, Danilo César. Universidade Federal de Pernambuco; Brasil
Fil: Tavares Cavalcanti Bedor, Noely Camila. No especifíca;
Fil: Wellithom Viturino da Silva, José. Universidade Federal de Pernambuco; Brasil
Fil: Damasceno Sousa, Giovana. Universidade Federal de Pernambuco; Brasil
Fil: Pereira de Santana, Davi. Universidade Federal de Pernambuco; Brasil
Fil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Blum, Bethania. No especifíca;
Fil: Alves, Fabiana. No especifíca;
Fil: Ribeiro, Isabela. No especifíca;
description Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng · ml1. Intra- and interday precision and bias values were less than 14.87% (n 9) and 9.81% (n 27), respectively. The recovery rates ranged from 94 to 100% with no matrix effect. There was no hematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for more than one year. This article describes the first microsampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and pediatric patients in remote areas and helps to address existing knowledge gaps in the treatment of CD.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/130191
Galindo Bedor, Danilo César ; Tavares Cavalcanti Bedor, Noely Camila ; Wellithom Viturino da Silva, José ; Damasceno Sousa, Giovana ; Pereira de Santana, Davi ; et al.; Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 62; 12; 12-2018; 1-12
0066-4804
CONICET Digital
CONICET
url http://hdl.handle.net/11336/130191
identifier_str_mv Galindo Bedor, Danilo César ; Tavares Cavalcanti Bedor, Noely Camila ; Wellithom Viturino da Silva, José ; Damasceno Sousa, Giovana ; Pereira de Santana, Davi ; et al.; Dried blood spot technique-based liquid chromatography-tandem mass spectrometry method as a simple alternative for benznidazole pharmacokinetic assessment; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 62; 12; 12-2018; 1-12
0066-4804
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.00845-18
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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 13.22299

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