Simultaneous determination of tectorigenin and its metabolites in rat plasma by ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry

• This is the first report to evaluate plasma pharmacokinetics of the conjugated metabolites in rats orally administered tectorigenin.
• Eight conjugated metabolites of tectorigenin in rat plasma were simultaneously determined using U-HPLC/Q-TOFMS method.
• The present study provides useful information for pharmacokinetic and pharmacodynamic investigations of isoflavones.

Tectorigenin is a major isoflavone found in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. It possesses hepatoprotective, estrogenic, hypoglycemic and anti-inflammatory activities. In the present study, the plasma pharmacokinetic profile of tectorigenin in rats was evaluated. We developed a selective and accurate U-HPLC/Q-TOFMS method for the simultaneous characterization of nine tectorigenin metabolites, and quantitation of six major metabolites in rat plasma, including tectorigenin-7-O-glucuronide-4′-O-sulfate (Te-7G-4′S), tectorigenin-di-O-sulfate (Te-diS), tectorigenin-7-O-glucuronide (Te-7G), tectorigenin-4′-O-glucuronide (Te-4′G), tectorigenin-7-O-sulfate (Te-7S) and tectorigenin after oral administration of tectorigenin (130 mg/kg). The plasma concentrations reached maximal values of 6.20 ± 2.05 μmol/L at 0.96 ± 0.68 h for Te-7G-4′S, 4.42 ± 1.36 μmol/L at 1.92 ± 2.15 h for Te-diS, 33.50 ± 4.89 μmol/L at 0.75 ± 0.67 h for Te-7G, 3.28 ± 1.01 μmol/L at 0.75 ± 0.67 h for Te-4′G, 12.80 ± 2.80 μmol/L at 0.85 ± 1.54 h for Te-7S, and 12.0 ± 0.63 μmol/L at 0.23 ± 0.15 h for tectorigenin, respectively. Enterohepatic recirculation resulted in double or triple peaks concentration curve/time profiles of the metabolites. Since the total plasma concentrations of tectorigenin conjugated metabolites were much higher than that of the tectorigenin aglycone, an extensive phase II metabolism plays an important role in the pharmacokinetics of tectorigenin in vivo.