Diverse positional 14C labeling-assisted metabolic analysis of pesticides in rats: The case of vanisulfane, a novel vanillin-derived pesticide

Information on pesticide metabolites is crucial for accurate environmental risk assessment. However, identifying the various metabolites of a novel pesticide is challenging since the potential metabolic pathways are unknown. In this study, we coupled diverse positional 14C labeling with high-resolution mass spectrometry to quantitatively and qualitatively study pesticide metabolism in rats. With the unique M/(M + 2) ratios derived from 14C, precursor compounds of metabolites could be better distinguished from impurity ions. Additionally, the use of diverse 14C labeling positions is a powerful tool to elucidate the complete metabolic fate of novel contaminants. Vanisulfane is a novel vanillin-derived antiviral agent with encouraging prospects for the efficient control of cucumber mosaic virus in China, but its metabolic pathways in mammals are still poorly understood. Thus, the metabolism of vanisulfane was studied in rats of both sexes by this strategy. The results showed that phase I and phase II metabolism occurred in both sexes. The former included mainly oxidation reactions, and the latter involved binding reactions that formed glucuronide, sulfate and amino acid conjugates. Sex-related differences were observed in the experiment, with earlier appearance of downstream metabolites and a preference for sulfate conjugate formation in males compared to females. This research facilitates the risk evaluation of vanisulfane, and offers an effective framework for screening unknown pesticide metabolic pathways, which could be applied to establish the metabolic profiles of other novel contaminants with limited information. [Display omitted] •14C labeling at diverse positions helps elucidate the complete metabolism.•Precursor ions with specific M/(M + 2) ratios facilitate metabolite identification.•The metabolism of vanisulfane has noteworthy sex-related differences.•Sulfate conjugate formation occurred preferentially in males compared to females.