Determination of Flavonol Metabolites in Plasma and Tissues of Rats by HPLC−Radiocounting and Tandem Mass Spectrometry Following Oral Ingestion of [2-14C]Quercetin-4‘-glucoside

Epidemiological studies suggest that consumption of flavonol-rich diets decreases the risk of developing heart disease and certain cancers. Recent studies have detected flavonol conjugates in blood and urine following various dietary interventions. To assess to what extent flavonols also accumulate in tissues, where they might be expected to exert anti-carcinogenic and anti-atherogenic effects, [2-14C]quercetin-4‘-glucoside was synthesized and fed to rats. After 60 min, 93.6% of the ingested radioactivity was recovered from the intestine, incorporated into 18 metabolites that had undergone deglycosylation followed by varying degrees of glucuronidation, methylation, and/or sulfation. [14C]Quercetin, the aglycon of the radiolabeled substrate, was present in the intestine and in trace amounts in the liver but was not detected in the plasma and kidneys. The original [2-14C]quercetin-4‘-glucoside was detected exclusively in the intestine, where it accounted for only 26.2% of the radioactivity. The remainder of the recovered radioactivity was located mainly in the plasma, liver, and kidneys as 14C-labeled metabolites. However, compared to the quantities in the gastrointestinal tract, the levels of metabolites in plasma and body tissues were very low, indicating only limited absorption into the blood stream. The data demonstrate that quercetin-4‘-glucoside, which is a major flavonol in onions, undergoes rapid and extensive metabolism in the intestine, and this appears not to be associated to any extent with transport across the gut wall into the blood stream. Keywords: [2-14C]Quercetin-4‘-glucoside; rat tissues; tandem mass spectrometry; methylated metabolites; glucuronides; sulfated derivatives