Toxicokinetics, Tissue Distribution, and Excretion of Dufulin Racemate and Its R ( S)-Enantiomers in Rats.

Abstract

Dufulin is a plant antiviral agent with a novel molecular structure and has been used widely to prevent and control tobacco and rice viral diseases. In this study, an UHPLC-MS/MS method was developed for rapid determination of dufulin racemate ( rac-DFL) and its R ( S)-enantiomers in rat plasma, tissues, urine, and feces. A MALDI-MSI method was further used for visual research on tissue distribution after intragastric administration of the three analytes. Toxicokinetic study showed that both ( R)-enantiomer of dufulin (( R)-DFL) and ( S)-enantiomer of dufulin (( S)-DFL) had a faster ability to reach Cmax than that of rac-DFL. ( R)-DFL and ( S)-DFL had a similar T1/2, though both were significantly lower than rac-DFL. Cmax of rac-DFL was obviously higher than ( R)-DFL or ( S)-DFL. Meanwhile, Cmax of ( S)-DFL was only about 60% of ( R)-DFL. Rac-DFL and its R ( S)-enantiomers had a dose-dependent toxicokinetic profile. Tissue distribution results revealed rac-DFL, ( R)-DFL, and ( S)-DFL mainly distributed in the liver and kidney, but the maximum concentration was only ng/g grade and could significantly degrade within 3 h. This indicates that dufulin does not cause liver and kidney toxicity in animals. In addition, rac-DFL and its R ( S)-enantiomers have not been detected in brain tissue. Cumulative excretion of rac-DFL and its R ( S)-enantiomers within 24 h in urine and feces were less than 22.85% indicating that they mainly excreted as metabolites. These results could provide evidence for the in-depth toxicity evaluation of dufulin pesticide. In addition, its metabolic selectivity information in vivo has also been obtained.