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

Autores
Marson, María Elena; Altcheh, Jaime; Moscatelli, Guillermo; Moroni, Samanta; Garcia-Bournissen, Facundo; Mastrantonio Garrido, Guido Enrique
Año de publicación
2015
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.
Facultad de Ciencias Exactas
Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico
Materia
Ciencias Exactas
Biología
Nitrocompounds
Benznidazole
N-benzylacetamide
Chagas disease
Metabolite
UPLC/MS/MS
Plasma
Pediatric pharmacology
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/130827

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network_name_str SEDICI (UNLP)
spelling Identification of N-benzylacetamide as a major component of human plasmatic metabolic profiling of benznidazoleMarson, María ElenaAltcheh, JaimeMoscatelli, GuillermoMoroni, SamantaGarcia-Bournissen, FacundoMastrantonio Garrido, Guido EnriqueCiencias ExactasBiologíaNitrocompoundsBenznidazoleN-benzylacetamideChagas diseaseMetaboliteUPLC/MS/MSPlasmaPediatric pharmacologyChagas disease is an endemic infection in Latin America with a high health impact. Caused by the parasite <i>Trypanosoma cruzi</i>, 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.Facultad de Ciencias ExactasPlanta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico2015-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf209-217http://sedici.unlp.edu.ar/handle/10915/130827enginfo:eu-repo/semantics/altIdentifier/issn/0378-7966info:eu-repo/semantics/altIdentifier/issn/2107-0180info:eu-repo/semantics/altIdentifier/doi/10.1007/s13318-014-0195-8info:eu-repo/semantics/altIdentifier/pmid/24711214info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-15T11:24:09Zoai:sedici.unlp.edu.ar:10915/130827Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-15 11:24:09.838SEDICI (UNLP) - Universidad Nacional de La Platafalse
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
Ciencias Exactas
Biología
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
Moscatelli, Guillermo
Moroni, Samanta
Garcia-Bournissen, Facundo
Mastrantonio Garrido, Guido Enrique
author Marson, María Elena
author_facet Marson, María Elena
Altcheh, Jaime
Moscatelli, Guillermo
Moroni, Samanta
Garcia-Bournissen, Facundo
Mastrantonio Garrido, Guido Enrique
author_role author
author2 Altcheh, Jaime
Moscatelli, Guillermo
Moroni, Samanta
Garcia-Bournissen, Facundo
Mastrantonio Garrido, Guido Enrique
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Exactas
Biología
Nitrocompounds
Benznidazole
N-benzylacetamide
Chagas disease
Metabolite
UPLC/MS/MS
Plasma
Pediatric pharmacology
topic Ciencias Exactas
Biología
Nitrocompounds
Benznidazole
N-benzylacetamide
Chagas disease
Metabolite
UPLC/MS/MS
Plasma
Pediatric pharmacology
dc.description.none.fl_txt_mv Chagas disease is an endemic infection in Latin America with a high health impact. Caused by the parasite <i>Trypanosoma cruzi</i>, 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.
Facultad de Ciencias Exactas
Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico
description Chagas disease is an endemic infection in Latin America with a high health impact. Caused by the parasite <i>Trypanosoma cruzi</i>, 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 2015
dc.date.none.fl_str_mv 2015-06
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info:eu-repo/semantics/publishedVersion
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info:eu-repo/semantics/altIdentifier/doi/10.1007/s13318-014-0195-8
info:eu-repo/semantics/altIdentifier/pmid/24711214
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
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