Pharmacokinetics and residue elimination of metalaxyl enantiomers in snakehead (Channa argus)

Abstract

Metalaxyl is widely used as a racemic mixture to control various plant and aquatic animal diseases caused by fungal infection. It has been proved that the two enantiomers of metalaxyl have significant differences in activity and toxicity, while little is known about the pharmacokinetics and residual elimination of the individual enantiomers of metalaxyl in aquatic animals. In this study, a simple, sensitive and reliable chiral liquid chromatography-tandem mass spectrometry method was established for the determination of metalaxyl and its metabolite metalaxyl acid enantiomers, which was applied to study the stereoselective pharmacokinetics and residue elimination of individual enantiomers in snakehead (Channa argus). The snakehead was bath administered with the racemic metalaxyl and the highly active enantiomeric R-metalaxyl, respectively. The results showed that the elimination of metalaxyl in the plasma and tissues of snakehead was enantioselective. The concentration of metalaxyl in tissues was kidney > liver > muscle, and preferential degradation of the R-metalaxyl enantiomer was observed in three tissues. However, no transformation between metalaxyl enantiomers was observed in snakehead plasma and tissues when R-metalaxyl enantiomer was administered. In addition, the distribution of metalaxyl acid enantiomers in tissues is closely related to the parent compound metalaxyl, and S-metalaxyl acid was only observed in the kidney and slowly eliminated. The highest concentrations of both metalaxyl and metalaxyl acid were observed in the kidney, suggesting that kidney is the major site of metalaxyl metabolism in snakehead. Given that the highly active R-metalaxyl has a shorter half-life and does not undergo transformation between enantiomers in snakehead, it may be a better choice to use R-metalaxyl instead of racemic metalaxyl in clinical practice. The results are helpful to understand the detailed fate of metalaxyl enantiomers and should be considered in future aquaculture, environmental pollution risk and food safety evaluations.