Fenamiphos is recalcitrant to the hydrolysis by alloforms PON1 Q192R of human serum

Abstract

Fenamiphos (ethyl 4-methylthio-m-tolyl isopropylphosphoramidate) is a racemic organophosphorus nematicide widely used in agriculture around the world. The paraoxonase 1 from human serum (PON1) is a phosphotriesterase (PTE) that hydrolyses several xenobiotics including drugs and organophosphorus compounds (OPs). In this work, the separation of the enantiomers of fenamiphos by HPLC using the column CHIRALCEL OJ and a mobile phase of hexane/ethanol (99/1) is presented. A liquid-liquid extraction method was implemented for the characterization of commercial nematicide hydrolysis by PON1 Q192R alloforms of human serum from children and adults. The results show a recovery of 94% for each isomer from the biological matrix. The method resulted linear response in a range concentration between 50 and 800μM with a detection and quantification limit between 0.6 and 2μM for the (+)-fenamiphos, and between 0.7 and 2.3μM for the (-)-fenamiphos. The levels of the Ca(2+)-dependent hydrolysis (residual concentration [μM]) quantified during 30min of reaction were only just 4-14% for both fenamiphos enantiomers with the three alloforms of PON1 Q192R of the two groups of serum studied. These results demonstrate that human serum PON1 is could be involved in the detoxification of a limited number of organophosphorus insecticides.