Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment

Autores
Marson, María Elena; García Bournissen, Facundo; Altcheh, Jaime; Moscatelli, Guillermo; Moroni, Samantha; Mastrantonio Garrido, Guido Enrique
Año de publicación
2020
Idioma
español castellano
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease is a serious public health problem in Latin America and, due to migration, in other nonendemic regions. Benznidazole (BNZ) is first choice drug in pediatric therapeutics. However, little is known regarding its metabolism in humans. The aim of the study was to isolate and identify products of human BZN metabolism in urine samples obtained from a pediatric Chagas patient and a healthy adult volunteer both treated with BZN. Urine samples were collected after dose of BNZ. Urine was treated with β-glucuronidase followed by an extraction procedure under two different pH conditions and a HPLC/UV and MS/MS identification of BZN and its metabolites. BZN (m/z 260.09847) was identified in all urine extracts. Peaks from each extracted chromatograms were selected for MS and MS/MS identification. Three compounds structurally related to BZN were identified: BZN-Na+ (m/z 283.08009), N-amine-BZN (m/z 230.12307) and N-hydroxi-amine-BZN (m/z 246.11702). BNZ-Na+ was identified in all extracts, but N-amine-BZN and N-hydroxi-amine-BZN were only observed in those extracts treated with β-glucuronidase. This is the first experimental report showing elimination of BZN N-reduced metabolites in urine. As they were released after treatment with β-glucuronidase it can be suggested that glucuronization plays a role in BNZ metabolism and renal elimination.
Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico
Materia
Química
Benznidazole metabolites
Chagas Disease/drug therapy
Glucuronidase/urine
High Performance Liquid Chromatography HPLC/methods
Mass Spectrometry/ methods
Antiparasitic agents/pharmacology
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/121849
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/121849
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatmentMarson, María ElenaGarcía Bournissen, FacundoAltcheh, JaimeMoscatelli, GuillermoMoroni, SamanthaMastrantonio Garrido, Guido EnriqueQuímicaBenznidazole metabolitesChagas Disease/drug therapyGlucuronidase/urineHigh Performance Liquid Chromatography HPLC/methodsMass Spectrometry/ methodsAntiparasitic agents/pharmacologyChagas disease is a serious public health problem in Latin America and, due to migration, in other nonendemic regions. Benznidazole (BNZ) is first choice drug in pediatric therapeutics. However, little is known regarding its metabolism in humans. The aim of the study was to isolate and identify products of human BZN metabolism in urine samples obtained from a pediatric Chagas patient and a healthy adult volunteer both treated with BZN. Urine samples were collected after dose of BNZ. Urine was treated with β-glucuronidase followed by an extraction procedure under two different pH conditions and a HPLC/UV and MS/MS identification of BZN and its metabolites. BZN (m/z 260.09847) was identified in all urine extracts. Peaks from each extracted chromatograms were selected for MS and MS/MS identification. Three compounds structurally related to BZN were identified: BZN-Na+ (m/z 283.08009), N-amine-BZN (m/z 230.12307) and N-hydroxi-amine-BZN (m/z 246.11702). BNZ-Na+ was identified in all extracts, but N-amine-BZN and N-hydroxi-amine-BZN were only observed in those extracts treated with β-glucuronidase. This is the first experimental report showing elimination of BZN N-reduced metabolites in urine. As they were released after treatment with β-glucuronidase it can be suggested that glucuronization plays a role in BNZ metabolism and renal elimination.Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/121849spainfo:eu-repo/semantics/altIdentifier/issn/2175-9790info:eu-repo/semantics/altIdentifier/doi/10.1590/s2175-97902019000218034info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-15T11:20:49Zoai:sedici.unlp.edu.ar:10915/121849Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-15 11:20:49.289SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
title Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
spellingShingle Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
Marson, María Elena
Química
Benznidazole metabolites
Chagas Disease/drug therapy
Glucuronidase/urine
High Performance Liquid Chromatography HPLC/methods
Mass Spectrometry/ methods
Antiparasitic agents/pharmacology
title_short Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
title_full Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
title_fullStr Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
title_full_unstemmed Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
title_sort Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
dc.creator.none.fl_str_mv Marson, María Elena
García Bournissen, Facundo
Altcheh, Jaime
Moscatelli, Guillermo
Moroni, Samantha
Mastrantonio Garrido, Guido Enrique
author Marson, María Elena
author_facet Marson, María Elena
García Bournissen, Facundo
Altcheh, Jaime
Moscatelli, Guillermo
Moroni, Samantha
Mastrantonio Garrido, Guido Enrique
author_role author
author2 García Bournissen, Facundo
Altcheh, Jaime
Moscatelli, Guillermo
Moroni, Samantha
Mastrantonio Garrido, Guido Enrique
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Química
Benznidazole metabolites
Chagas Disease/drug therapy
Glucuronidase/urine
High Performance Liquid Chromatography HPLC/methods
Mass Spectrometry/ methods
Antiparasitic agents/pharmacology
topic Química
Benznidazole metabolites
Chagas Disease/drug therapy
Glucuronidase/urine
High Performance Liquid Chromatography HPLC/methods
Mass Spectrometry/ methods
Antiparasitic agents/pharmacology
dc.description.none.fl_txt_mv Chagas disease is a serious public health problem in Latin America and, due to migration, in other nonendemic regions. Benznidazole (BNZ) is first choice drug in pediatric therapeutics. However, little is known regarding its metabolism in humans. The aim of the study was to isolate and identify products of human BZN metabolism in urine samples obtained from a pediatric Chagas patient and a healthy adult volunteer both treated with BZN. Urine samples were collected after dose of BNZ. Urine was treated with β-glucuronidase followed by an extraction procedure under two different pH conditions and a HPLC/UV and MS/MS identification of BZN and its metabolites. BZN (m/z 260.09847) was identified in all urine extracts. Peaks from each extracted chromatograms were selected for MS and MS/MS identification. Three compounds structurally related to BZN were identified: BZN-Na+ (m/z 283.08009), N-amine-BZN (m/z 230.12307) and N-hydroxi-amine-BZN (m/z 246.11702). BNZ-Na+ was identified in all extracts, but N-amine-BZN and N-hydroxi-amine-BZN were only observed in those extracts treated with β-glucuronidase. This is the first experimental report showing elimination of BZN N-reduced metabolites in urine. As they were released after treatment with β-glucuronidase it can be suggested that glucuronization plays a role in BNZ metabolism and renal elimination.
Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico
description Chagas disease is a serious public health problem in Latin America and, due to migration, in other nonendemic regions. Benznidazole (BNZ) is first choice drug in pediatric therapeutics. However, little is known regarding its metabolism in humans. The aim of the study was to isolate and identify products of human BZN metabolism in urine samples obtained from a pediatric Chagas patient and a healthy adult volunteer both treated with BZN. Urine samples were collected after dose of BNZ. Urine was treated with β-glucuronidase followed by an extraction procedure under two different pH conditions and a HPLC/UV and MS/MS identification of BZN and its metabolites. BZN (m/z 260.09847) was identified in all urine extracts. Peaks from each extracted chromatograms were selected for MS and MS/MS identification. Three compounds structurally related to BZN were identified: BZN-Na+ (m/z 283.08009), N-amine-BZN (m/z 230.12307) and N-hydroxi-amine-BZN (m/z 246.11702). BNZ-Na+ was identified in all extracts, but N-amine-BZN and N-hydroxi-amine-BZN were only observed in those extracts treated with β-glucuronidase. This is the first experimental report showing elimination of BZN N-reduced metabolites in urine. As they were released after treatment with β-glucuronidase it can be suggested that glucuronization plays a role in BNZ metabolism and renal elimination.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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info:ar-repo/semantics/articulo
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status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/121849
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dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/2175-9790
info:eu-repo/semantics/altIdentifier/doi/10.1590/s2175-97902019000218034
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
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