Stereoselective Toxicokinetic and Distribution Study on the Hexaconazole Enantiomers in Mice

Author:

Luo Guofei1,Pang Junxiao2,Sun Dali1,Zhang Qinghai1

Affiliation:

1. The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, China

2. Food and Pharmaceutical Engineering Institute, Guiyang University, Guiyang 550005, China

Abstract

Hexaconazole (Hex) has been widely used in agricultural products, and its residues may pose a potential risk to human health. However, the metabolic behavior of Hex enantiomers in mammal organisms is still unknown, which is important for evaluating the differences in their toxicity. In this study, the distribution of S-(+)- and R-(−)-Hex in mice was detected by an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS), and the mechanism differences in the toxicokinetic behavior were analyzed by molecular docking. Good linearities, accuracies, and precisions were achieved for S-(+)- and R-(−)-Hex, with recoveries of 88.7~104.2% and RSDs less than 9.45% in nine tissues of mice. This established method was then used to detect the toxicokinetic of Hex enantiomers in mice after oral administration within 96 h. The results showed that the half-lives of S-(+)- and R-(−)-Hex were 3.07 and 3.71 h in plasma. Hex was mainly accumulated in the liver, followed by the kidneys, brain, lungs, spleen, and heart. The enantiomeric fraction (EF) values of Hex enantiomers in most of the samples were below 1, indicating that S-(+)-Hex decreased faster than its antipode. The molecular docking showed that the binding of S-(+)-Hex with P450arom was much more stable than R-(−)-Hex, which verified the fact that S-(+)-Hex was prefer to decrease in most of the tissues. The results of this study could be helpful for further evaluating the potential toxic risk of Hex enantiomers and for the development and usage of its pure monomer.

Funder

National Natural Science Foundation of China

Guizhou Provincial Department of Education Project

Guizhou Provincial Health Commission Project

Engineering Research Center of Higher Education Institutions in Guizhou province

Publisher

MDPI AG

Subject

Chemical Health and Safety,Health, Toxicology and Mutagenesis,Toxicology

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