Development of a novel LC-MS/MS method for quantitation of triticonazole enantiomers in rat plasma and tissues and application to study on toxicokinetics and tissue distribution

摘要

Triticonazole with an asymmetrical carbon atom has two enantiomers and is a broad-spectrum systemic fungicide, but its disposition in animals is unclear. In this study, a chiral analytical method of LC-MS/MS was developed and validated for the assay of triticonazole enantiomers in rat plasma and tissues. There were no endogenous interferences in the blank plasma and tissues of rats. R-(-)- and S-(+)-triticonazole peaks were separated entirely. The calibration curves were linear from 25 to 2500 ng/mL of each enantiomer. The accuracy, precision, and stability met the requirements of bioanalysis. Therefore, this method is enantioselective, accurate, precise, sensitive and reliable, and has been successfully applied to analyze R-(-)- and S-(+)-triticonazole in rat plasma and to study the toxicokinetics of triticonazole enantiomers in rats. After single oral administration of 50 mg/kg racemate triticonazole to rats, the AUC((0-infinity)) and C-max of R-(-)-triticonazole were 3.5 and 3.6 times higher than that of S-(+)-triticonazole, respectively. The content of S-(+)-triticonazole was higher in the kidney whilst R-(-)-triticonazole was higher in the brain and small intestine. The results showed that the toxicokinetics and tissues distribution of triticonazole enantiomers in rats have stereoselective differences. (C) 2019 Published by Elsevier B.V.