Summary: | A reliable high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established for the simultaneous detection of zearalenone-14-glucoside (ZEN-14G) and its metabolite, zearalenone (ZEN), in the plasma, urine, and various tissues of rats. The performance of the developed method was validated by determining the selectivity, linearity (<i>R</i><sup>2</sup> > 0.99), sensitivity (lower limit of quantification, 0.1–1 μg/L), recovery (80.7 ± 3.0–112.3 ± 3.1%), precision (0.6–16.5%), and stability (81.7 ± 1.7–104.1 ± 3.9%). Through use of the methodological advances, the subsequent kinetics and distribution after administration of ZEN-14G by gavage were thoroughly investigated. ZEN-14G and ZEN exhibited similar trends in the plasma, and reached their peak concentrations at 10 min and then rapidly decreased. ZEN-14G could be quantified in the stomach, small intestine, and large intestine 24 h after administration, while ZEN was detectable in all tested tissues. Interestingly, ZEN-14G (7.6 ± 3.0 μg/L) and ZEN (977.5 ± 98.0 μg/L) were also detected in the urine 24 h after administration, indicating that ZEN-14G was prone to be slowly and continuously hydrolyzed into ZEN to be absorbed into the plasma and distributed to various tissues, thus leading to a cumulative exposure. Continuous attention should be paid to the co-exposure of ZEN and ZEN-14G, which might pose additional health risks to humans and animals.
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