Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5135638 | Journal of Chromatography A | 2016 | 35 Pages |
Abstract
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 (â)-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 â Chiralpak AS-H); hexane: ethanol: methanol (85:12:3, v/v/v) was used as mobile phase at a flow rate of 1.2Â mLÂ minâ1. 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.
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Nayara Cristina Perez de Albuquerque, Juliana Vicentin de Matos, Anderson Rodrigo Moraes de Oliveira,