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Biotransformation and Quantification of Sinensetin and Its Metabolites in Plasma, Urine, and Feces of Rats.

As one of the major polymethoxyflavones in citrus peels, sinensetin (Sin) has been reported to possess numerous bioactivities. However, its detailed in vivo metabolic fate has not been uncovered yet. In the present study, the possible metabolites of Sin were synthesized, and all five mono-demethylated metabolites were successfully identified via ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis in rats fed with 100 mg/(kg·bw) Sin. The excretion and pharmacokinetic studies were then carried out to quantitatively investigate their variation in content with time in urine, feces, and plasma samples. Results showed that 4'-demethylsinensetin, 6-demethylsinensetin, and 3'-demethylsinensetin were the three most abundant metabolites generated in the above-mentioned biological samples. In addition, the total amount of Sin with its metabolites showed a significantly higher content in urine than in feces, indicating that Sin may be easily absorbed in the small intestine.