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

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

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.

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Abbreviations

Te:

Tectorigenin

Iso-Te:

Isotectorigenin

Te-7G-4′S:

Tectorigenin-7-O-glucuronide-4′-sulfate

Te-7G:

Tectorigenin-7-O-glucuronide

Te-4′G:

Tectorigenin-4′-O-glucuronide

Te-7S:

Tectorigenin-7-O-sulfate

Te-4′S:

Tectorigenin-4′-O-sulfate

Te-diG:

Tectorigenin-7-O-glucuronide-4′-glucuronide

Te-diS:

Tectorigenin-7-O-sulfate-4′-sulfate

Ir:

Irisolidone

Ir-7G:

Irisolidone-7-O-glucuronide

Demethoxyl-Te-G:

Demethoxyl-tectorigenin-glucuronide

Demethoxyl-Te-S:

Demethoxyl-tectorigenin-sulfate

Dehydroxyl-Te-G:

Dehydroxyl-tectorigenin-glucuronide

Demethyl-Te-diG:

Demethyl-tectorigenin-diglucuronide

Demethyl-Te-G:

Demethyl-tectorigenin-glucuronide

Methoxyl-Te:

Methoxyl-tectorigenin

Hydroxyl-Te-G-S:

Hydroxyl-tectorigenin-glucuronide-sulfate

Hydroxyl-Te-G:

Hydroxyl-tectorigenin-glucuronide

Hydroxyl-Te-S:

Hydroxyl-tectorigenin-sulfate

Hydroxyl-Te-diG:

Hydroxyl-tectorigenin-diglucuronide

UGTs:

UDP-glucuronosyltransferases

UDPGA:

UDP-glucuronic acid

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Acknowledgments

This work was financially supported by the Research Fund for the Doctoral Program of Higher Education, China (No.200801630007), the 2008 Scientific Technology Plan Project from Science and Technology Department of Liaoning Province, China (No. 20082260233), and the central financial support to the local provincial key disciplines of special fund, and distinguished professor fund of Liaoning province of 2011.

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The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China

    Ziming Shi, Guozhe Zhang, Lizhu Zhao, Shen Wang, Yoshihiro Kano & Dan Yuan

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  1. Ziming Shi
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  2. Guozhe Zhang
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  3. Lizhu Zhao
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  4. Shen Wang
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  5. Yoshihiro Kano
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  6. Dan Yuan
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Correspondence to Dan Yuan.

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Shi, Z., Zhang, G., Zhao, L. et al. Excretion of tectorigenin in rat urine orally administrated at different dosages by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Eur J Drug Metab Pharmacokinet 40, 255–266 (2015). https://doi.org/10.1007/s13318-014-0202-0

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