Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole

Autores
Marson, María Elena; Altcheh, Jaime Marcelo; Moscatelli, Guillermo; Moroni, Samanta; García Bournissen, Facundo; Mastrantonio Garrido, Guido Enrique
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease is an endemic infection in Latin America with a high health impact. Caused by the parasite Trypanosoma cruzi, it has expanded to non-endemic regions such as North America and European countries via immigration of infected people. This infectious disease has been rising in the ranking of international health priorities due to the growing migration flows from endemic to non-endemic areas. Benznidazole (BZN), a nitroheterocyclic drug, is one of the two trypanocidal drugs currently in clinical use, associated with significant adverse drug reactions (ADRs). Mammalian metabolism of BNZ has been poorly studied, including the potential role of metabolites on both toxicity and anti-parasitic activity. High-resolution UPLC/MS/MS was used to analyze three plasma samples obtained from pediatric patients under BNZ treatment in steady state. Spectroscopic and structural criteria were applied to identify BNZ and accompanying substances from chromatographic signals. From all detected species, two can be undoubtedly associated with the BNZ and N-benzylacetamide molecules, the second one being a fragment of the parent drug (BZN). From the obtained results, two hypotheses could be formulated. The first one is to relate the presence of N-benzyl acetamide with the hepatic metabolism of BNZ. The second hypothesis has to do with the possible trypanocidal activity of this metabolite, as well as its role in the development of side effects, associated with the pharmacotherapy. Complementary studies should be carried out to determine the possible association of this metabolite with the BNZ treatment stages, patient’s clinical features, ADRs, and trypanocidal effectiveness.
Fil: Marson, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Planta Piloto Multipropósito; Argentina
Fil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Moscatelli, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Planta Piloto Multipropósito; Argentina
Materia
Nitrocompounds
Benznidazole
N-Benzylacetamide
Chagas Disease
Metabolite
Uplc/Ms/Ms
Plasma
Pediatric Pharmacology
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:11336/32547
Acceder
id CONICETDig_d83bba48af9f5b3f23f5d6b51c1bd409
oai_identifier_str oai:ri.conicet.gov.ar:11336/32547
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazoleMarson, María ElenaAltcheh, Jaime MarceloMoscatelli, GuillermoMoroni, SamantaGarcía Bournissen, FacundoMastrantonio Garrido, Guido EnriqueNitrocompoundsBenznidazoleN-BenzylacetamideChagas DiseaseMetaboliteUplc/Ms/MsPlasmaPediatric Pharmacologyhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Chagas disease is an endemic infection in Latin America with a high health impact. Caused by the parasite Trypanosoma cruzi, it has expanded to non-endemic regions such as North America and European countries via immigration of infected people. This infectious disease has been rising in the ranking of international health priorities due to the growing migration flows from endemic to non-endemic areas. Benznidazole (BZN), a nitroheterocyclic drug, is one of the two trypanocidal drugs currently in clinical use, associated with significant adverse drug reactions (ADRs). Mammalian metabolism of BNZ has been poorly studied, including the potential role of metabolites on both toxicity and anti-parasitic activity. High-resolution UPLC/MS/MS was used to analyze three plasma samples obtained from pediatric patients under BNZ treatment in steady state. Spectroscopic and structural criteria were applied to identify BNZ and accompanying substances from chromatographic signals. From all detected species, two can be undoubtedly associated with the BNZ and N-benzylacetamide molecules, the second one being a fragment of the parent drug (BZN). From the obtained results, two hypotheses could be formulated. The first one is to relate the presence of N-benzyl acetamide with the hepatic metabolism of BNZ. The second hypothesis has to do with the possible trypanocidal activity of this metabolite, as well as its role in the development of side effects, associated with the pharmacotherapy. Complementary studies should be carried out to determine the possible association of this metabolite with the BNZ treatment stages, patient’s clinical features, ADRs, and trypanocidal effectiveness.Fil: Marson, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Planta Piloto Multipropósito; ArgentinaFil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Moscatelli, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; ArgentinaFil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Planta Piloto Multipropósito; ArgentinaMedecine Et Hygiene2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32547Marson, María Elena; Altcheh, Jaime Marcelo; Moscatelli, Guillermo; Moroni, Samanta; García Bournissen, Facundo; et al.; Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole; Medecine Et Hygiene; European Journal Of Drug Metabolism And Pharmacokinetics; 40; 2; 4-2014; 209-2170378-7966CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs13318-014-0195-8info:eu-repo/semantics/altIdentifier/doi/10.1007/s13318-014-0195-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:02Zoai:ri.conicet.gov.ar:11336/32547instacron: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:34982025-09-03 09:55:02.915CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole
title Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole
spellingShingle Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole
Marson, María Elena
Nitrocompounds
Benznidazole
N-Benzylacetamide
Chagas Disease
Metabolite
Uplc/Ms/Ms
Plasma
Pediatric Pharmacology
title_short Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole
title_full Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole
title_fullStr Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole
title_full_unstemmed Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole
title_sort Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole
dc.creator.none.fl_str_mv Marson, María Elena
Altcheh, Jaime Marcelo
Moscatelli, Guillermo
Moroni, Samanta
García Bournissen, Facundo
Mastrantonio Garrido, Guido Enrique
author Marson, María Elena
author_facet Marson, María Elena
Altcheh, Jaime Marcelo
Moscatelli, Guillermo
Moroni, Samanta
García Bournissen, Facundo
Mastrantonio Garrido, Guido Enrique
author_role author
author2 Altcheh, Jaime Marcelo
Moscatelli, Guillermo
Moroni, Samanta
García Bournissen, Facundo
Mastrantonio Garrido, Guido Enrique
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Nitrocompounds
Benznidazole
N-Benzylacetamide
Chagas Disease
Metabolite
Uplc/Ms/Ms
Plasma
Pediatric Pharmacology
topic Nitrocompounds
Benznidazole
N-Benzylacetamide
Chagas Disease
Metabolite
Uplc/Ms/Ms
Plasma
Pediatric Pharmacology
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chagas disease is an endemic infection in Latin America with a high health impact. Caused by the parasite Trypanosoma cruzi, it has expanded to non-endemic regions such as North America and European countries via immigration of infected people. This infectious disease has been rising in the ranking of international health priorities due to the growing migration flows from endemic to non-endemic areas. Benznidazole (BZN), a nitroheterocyclic drug, is one of the two trypanocidal drugs currently in clinical use, associated with significant adverse drug reactions (ADRs). Mammalian metabolism of BNZ has been poorly studied, including the potential role of metabolites on both toxicity and anti-parasitic activity. High-resolution UPLC/MS/MS was used to analyze three plasma samples obtained from pediatric patients under BNZ treatment in steady state. Spectroscopic and structural criteria were applied to identify BNZ and accompanying substances from chromatographic signals. From all detected species, two can be undoubtedly associated with the BNZ and N-benzylacetamide molecules, the second one being a fragment of the parent drug (BZN). From the obtained results, two hypotheses could be formulated. The first one is to relate the presence of N-benzyl acetamide with the hepatic metabolism of BNZ. The second hypothesis has to do with the possible trypanocidal activity of this metabolite, as well as its role in the development of side effects, associated with the pharmacotherapy. Complementary studies should be carried out to determine the possible association of this metabolite with the BNZ treatment stages, patient’s clinical features, ADRs, and trypanocidal effectiveness.
Fil: Marson, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Planta Piloto Multipropósito; Argentina
Fil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Moscatelli, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina
Fil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Planta Piloto Multipropósito; Argentina
description Chagas disease is an endemic infection in Latin America with a high health impact. Caused by the parasite Trypanosoma cruzi, it has expanded to non-endemic regions such as North America and European countries via immigration of infected people. This infectious disease has been rising in the ranking of international health priorities due to the growing migration flows from endemic to non-endemic areas. Benznidazole (BZN), a nitroheterocyclic drug, is one of the two trypanocidal drugs currently in clinical use, associated with significant adverse drug reactions (ADRs). Mammalian metabolism of BNZ has been poorly studied, including the potential role of metabolites on both toxicity and anti-parasitic activity. High-resolution UPLC/MS/MS was used to analyze three plasma samples obtained from pediatric patients under BNZ treatment in steady state. Spectroscopic and structural criteria were applied to identify BNZ and accompanying substances from chromatographic signals. From all detected species, two can be undoubtedly associated with the BNZ and N-benzylacetamide molecules, the second one being a fragment of the parent drug (BZN). From the obtained results, two hypotheses could be formulated. The first one is to relate the presence of N-benzyl acetamide with the hepatic metabolism of BNZ. The second hypothesis has to do with the possible trypanocidal activity of this metabolite, as well as its role in the development of side effects, associated with the pharmacotherapy. Complementary studies should be carried out to determine the possible association of this metabolite with the BNZ treatment stages, patient’s clinical features, ADRs, and trypanocidal effectiveness.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
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/11336/32547
Marson, María Elena; Altcheh, Jaime Marcelo; Moscatelli, Guillermo; Moroni, Samanta; García Bournissen, Facundo; et al.; Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole; Medecine Et Hygiene; European Journal Of Drug Metabolism And Pharmacokinetics; 40; 2; 4-2014; 209-217
0378-7966
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32547
identifier_str_mv Marson, María Elena; Altcheh, Jaime Marcelo; Moscatelli, Guillermo; Moroni, Samanta; García Bournissen, Facundo; et al.; Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazole; Medecine Et Hygiene; European Journal Of Drug Metabolism And Pharmacokinetics; 40; 2; 4-2014; 209-217
0378-7966
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://link.springer.com/article/10.1007%2Fs13318-014-0195-8
info:eu-repo/semantics/altIdentifier/doi/10.1007/s13318-014-0195-8
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Medecine Et Hygiene
publisher.none.fl_str_mv Medecine Et Hygiene
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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