Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment
| Autor: | Facundo García Bournissen, Jaime Altcheh, María Elena Marson, Guido Mastrantonio, Guillermo Moscatelli, Samantha Moroni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Chagas disease
Urine Pediatrics 030226 pharmacology & pharmacy 01 natural sciences High-performance liquid chromatography 03 medical and health sciences Chagas Disease/drug therapy Pharmacy and materia medica 0302 clinical medicine medicine Volunteer Glucuronidase/urine Mass Spectrometry/ methods Chromatography Chemistry Benznidazole metabolites Metabolism Química High Performance Liquid Chromatography HPLC/methods medicine.disease 0104 chemical sciences Glucuronidase RS1-441 010404 medicinal & biomolecular chemistry Renal Elimination Benznidazole Antiparasitic agents/pharmacology medicine.drug |
| Zdroj: | Brazilian Journal of Pharmaceutical Sciences, Volume: 56, Article number: e18034, Published: 16 MAR 2020 Brazilian Journal of Pharmaceutical Sciences; Vol. 56 (2020); e18034 Brazilian Journal of Pharmaceutical Sciences; v. 56 (2020); e18034 Brazilian Journal of Pharmaceutical Sciences Universidade de São Paulo (USP) instacron:USP Paediatrics Publications SEDICI (UNLP) Universidad Nacional de La Plata instacron:UNLP Brazilian Journal of Pharmaceutical Sciences, Vol 56 (2020) |
| ISSN: | 2175-9790 1984-8250 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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