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Updated: Aug 15, 2026
Semi-Targeted Ultra-High-Performance Chromatography Coupled to Mass Spectrometry Analysis of Phenolic Metabolites in Plasma of Elderly Adults
Published on: April 22, 2022
Pharmacokinetics of dietary phenethyl isothiocyanate in rats
Yan Ji1, Yuhsin Kuo, Marilyn E Morris
1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York at Buffalo, 517 Hochstetter Hall, Amherst, New York, 14260, USA.
Purpose:
Phenethyl isothiocyanate (PEITC) is a dietary component present in cruciferous vegetables and reported to have chemopreventive properties. Previous reports of PEITC pharmacokinetics have measured total ITC (PEITC and its metabolites) in plasma. Our objective was to examine the dose-dependent pharmacokinetics and oral bioavailability of unchanged PEITC, as well as its pH- and temperature-dependent stability and its serum protein binding.
Methods:
Stability was studied at different pH values at room temperature and 4 degrees C. Protein binding was determined by equilibrium dialysis. For the pharmacokinetics study, male Sprague-Dawley rats were administered with PEITC at doses of 2, 10, 100, or 400 micromol/kg intravenously or 10 or 100 micromol/kg orally. Plasma samples were analyzed by liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was conducted by WinNonlin and ADAPT II.
Results:
Phenethyl isothiocyanate was stable in aqueous buffers at pH 7.4 with half-lives of 56.1 and 108 h at room temperature and 4 degrees C, respectively. The free fraction of PEITC in rat serum was 0.019. The clearance (Cl) at a low dose of PEITC (2 micromol/kg) was 0.70 +/- 0.17 L h(-1) kg(-1) with an apparent volume of distribution (Vss) of 1.94 +/- 0.42 L/kg. At higher doses, Cl tended to decrease, whereas Vss increased. Oral bioavailability of PEITC was 115 and 93% at doses of 10 and 100 micromol/kg, respectively. A three-compartment model with Michaelis-Menten elimination and distribution was found to best characterize the plasma concentration profiles.
Conclusions:
Phenethyl isothiocyanate is stable in biological samples, with increased stability under refrigerated conditions. It has high oral bioavailability, low clearance, and high protein binding in rats; nonlinear elimination and distribution occur following the administration of high doses. This investigation represents the first report of the pharmacokinetics of dietary PEITC.
