Excretion of tectorigenin in rat urine orally administrated at different dosages by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

• Published in: European journal of drug metabolism and pharmacokinetics Vol. 40; no. 3; pp. 255 - 266
• Main Authors: Shi, Ziming, Zhang, Guozhe, Zhao, Lizhu, Wang, Shen, Kano, Yoshihiro, Yuan, Dan
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2015
• Subjects: Administration, Oral; Animals; Biomedical and Life Sciences; Biomedicine; Chromatography, High Pressure Liquid - methods; Flavonoids - metabolism; Genistein - metabolism; Glucuronides - metabolism; Human Physiology; Isoflavones - administration & dosage; Isoflavones - metabolism; Isoflavones - urine; Male; Mass Spectrometry - methods; Medical Biochemistry; Original Paper; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacy; Pueraria - chemistry; Rats; Rats, Sprague-Dawley; Rhizome - chemistry; Urine; Excretion; Glucuronidation; Rat; UHPLC/Q-TOFMS; Tectorigenin
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/s13318-014-0202-0

Tectorigenin (Te) is a main active component in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Previously, we have reported the pharmacokinetic properties of Te in rat plasma. The purpose of this study was to investigate the urinary excretion of Te after oral administration to rats at different dose levels. Using UHPLC/Q-TOFMS, totally 26 metabolites were detected in rat urine after oral administration of Te at dose of 65 and 130 mg/kg. Among them, nine metabolites, Te, tectorigenin-7- O -glucuronide-4′-sulfate (Te-7G-4′S), tectorigenin-7- O -glucuronide (Te-7G), tectorigenin-7- O -sulfate (Te-7S), tectorigenin-4′- O -glucuronide (Te-4′S), isotectorigenin, genistein, irisolidone-7- O -glucuronide (Ir-7G), and irisolidone, were identified by comparing the retention time, UV and MS spectra with those of authentic standards. A UHPLC/Q-TOFMS method for simultaneous quantification and semi-quantification of all the metabolites in urine was developed. The cumulative urinary excretions of Te and the major metabolite Te-7G were 1.99 and 5.80 μmol at 65 mg/kg, 3.05 and 6.48 μmol at 130 mg/kg, accounted for 4.17 % and 15.8, 2.81 and 9.49 % of administrated Te, respectively. The excretion rates of Te-7G, Te-7G-4′S, Ir-7G, and Te reached a maximum between 12 and 24 h after oral dosing at 65 and 130 mg/kg. The cumulative urine excretion rates of Te were 23.1 and 20.1 % within 72 h at 65 and 130 mg/kg, respectively. These results suggested that the glucuronidation was the primary metabolic pathway especially at low dose level.