Pharmacokinetics of conjugated metabolites in rat plasma after oral administration of tectoridin

Tectoridin is a major isoflavone found in the flowers of Pueraria thomsonii Benth. It possesses estrogenic, hypoglycemic, anti-oxidant, and anti-inflammatory activities. In the present study, we evaluated the plasma pharmacokinetic profile of tectoridin in rats. We isolated a new metabolite, tectorigenin-7-O-glucuronide-4′-O-sulfate (Te-7G-4′S), from the bile of rats treated orally with tectoridin and determined its chemical structure by spectral analysis. Furthermore, we developed a selective and accurate method for the simultaneous quantification of tectoridin metabolites, including Te-7G-4′S, tectorigenin-7-O-glucuronide (Te-7G), tectorigenin-7-O-sulfate (Te-7S), and tectorigenin in rat plasma, and measured their plasma concentrations in rats orally administered tectoridin (200 mg/kg). Plasma concentrations of Te-7G-4′S, Te-7G, Te-7S, and tectorigenin reached maximal values of 21.4 ± 13.8 μmol at 3.50 ± 1.87 h, 20.5 ± 9.7 μmol at 3.17 ± 1.81 h, 14.3 ± 3.3 μmol at 5.58 ± 3.07 h, and 8.67 ± 3.07 μmol at 4.92 ± 2.87 h, respectively. Enterohepatic recirculation resulted in double peaks or a flat concentration curve/time profile of the metabolites. Since plasma concentrations of tectorigenin conjugated metabolites were higher than those of the tectorigenin aglycone, it can be concluded that extensive phase II metabolism plays an important role in the pharmacokinetics of tectoridin and tectorigenin in vivo.

► A new glucuronide-sulfate diconjugate was isolated and structurally determined for the first time.
► Three conjugate metabolites were simultaneously identified and quantified in rat plasma by HPLC–DAD and LC/TOF/MS.
► It provides helpful information for the potential therapeutic application of tectoridin-containing phytopharmacueticals.