In-line coupling of an achiral-chiral column to investigate the enantioselective in vitro metabolism of the pesticide Fenamiphos by human liver microsomes

Autor(es)

Perez de Albuquerque, Nayara Cristina ; de Matos, Juliana Vicentin ; Moraes de Oliveira, Anderson Rodrigo

• Tipo de documento: Artigo Científico
• Fonte: Journal of Chromatography A; v. 1467, p. 326-334, OCT 7 2016.
• Citações Web of Science: 6

Resumo

The distinct activity and toxicity of enantiomers has increased concern about the use of chiral pesticides. The chiral pesticide Fenamiphos (FS) is employed as a racemic mixture to control nematode pests. Although recent studies revealed that FS enantiomers possess different toxicity, the toxicokinetics and liver metabolism of these enantiomers in humans remain unclear. This study characterizes the in vitro metabolism of rac-FS, (+)-FS, and (-)-FS by human liver microsomes and predicts some toxicokinetic parameters. First, a new enantioselective HPLC method was developed to analyze FS and its metabolites {[}fenamiphos sulfoxide (FSO) and fenamiphos sulfone (FSO2)]. Chiral separation of the stereoisomers was accomplished in an in-line coupled achiral-chiral column (Lichrosorb Si60 Chiralpak AS-H); hexane: ethanol: methanol (85:12:3, v/v/v) was used as mobile phase at a flow rate of 1.2 mL min(-1). Then, the HPLC method was fully validated. All the evaluated parameters agreed with the European Medicines Agency guideline. Finally, the enantioselective kinetic parameters were determined for CYP450 enzymes. The predicted toxicokinetic parameters showed that the liver exclusively eliminated FS without stereoselectivity. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 15/02533-1 - Estudos enantiosseletivos de metabolismo, citotoxicidade e genotoxicidade in vitro do nematicida Fenamifós
• Beneficiário: Nayara Cristina Perez de Albuquerque
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/07597-0 - Desenvolvimento de métodos cromatográficos/eletroforéticos para posterior aplicação em estudos in vitro de inibição enzimática e interações medicamentosas de pesticidas quirais
• Beneficiário: Anderson Rodrigo Moraes de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular