RESUMEN
Monitoring the drug benznidazole in biological fluids is a powerful tool for clinical diagnostic and pharmacological studies in chagasic patients. However, research in this concern needs to be done. The accurate quantitation of this drug in complex matrices represents a highly challenging task complicated by the absence of sensitive analytical methods. It follows that sample processing strategies, preparation/cleanup procedures, and chromatographic/ionization/detection parameters, were evaluated for method optimization. The summation of this work generated a rapid, selective, sensitive methodology based on reversed-phase chromatography-tandem mass spectrometry for the analysis of benznidazole in urine samples. To the best of our knowledge, this is a first report of a LC-MS/MS platform employed for this application. Matrix effect was determined; a 90% of signal suppression was observed. The limits of detection and quantification were 0.75 and 4.85 µg L(-1); respectively. The latter allowed the method's application to the detection of benznidazole in clinical studies and pharmacological monitoring analysis.
Asunto(s)
Enfermedad de Chagas/orina , Cromatografía Liquida/métodos , Nitroimidazoles/orina , Espectrometría de Masas en Tándem/métodos , Tripanocidas/orina , Niño , Humanos , Extracción Líquido-Líquido/métodos , Nitroimidazoles/aislamiento & purificación , Tripanocidas/aislamiento & purificaciónRESUMEN
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.