Absorption, disposition, metabolism, and excretion of [3- ¹⁴C]caffeic acid in rats

Male Sprague-Dawley rats ingested 140 ×10⁶ dpm of [3- ¹⁴C]trans-caffeic acid, and over the ensuing 72 h period, body tissues, plasma, urine, and feces were collected and the overall levels of radioactivity determined. Where sufficient radioactivity had accumulated, samples were analyzed by HPLC with online radioactivity and tandem mass spectrometric detection. Nine labeled compounds were identified, the substrate and its cis isomer, 3′-O- and 4′-O-sulfates and glucuronides of caffeic acid, 4′-O-sulfates and glucuronides of ferulic acid, and isoferulic acid-4′-O-sulfate. Four unidentified metabolites were also detected. After passing down the gastrointestinal tract, the majority of the radiolabeled metabolites were excreted in urine with minimal accumulation in plasma. Only relatively small amounts of an unidentified ¹⁴C-labeled metabolite were expelled in feces. There was little or no accumulation of radioactivity in body tissues, including the brain. The overall recovery of radioactivity 72 h after ingestion of [3-¹⁴C]caffeic acid was ∼80% of intake.