PHARMACOKINETICS, BIOAVAILABILITY, AND METABOLISM OF 2,3,5,4′-TETRAHYDROXYSTILBENE-2-O-β-D-GLUCOSIDE IN RATS BY ULTRA-PERFORMANCE LIQUID CHROMATOGRAPHY–QUADRUPOLE TIME-OF-FLIGHT MASS SPECTROMETRY AND HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY-ULTRAVIOLET DETECTION

Abstract

2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (THSG), a natural product purified from the Chinese medical herb Polygoni multiflori Radix, has been demonstrated to possess many pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, and antitumor properties. Ultra-performance liquid chromatography–time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and high-performance liquid chromatography-ultraviolet detection (HPLC-UV) methods were developed for the pharmacokinetics, bioavailability, absorption, and metabolism studies of THSG in rats following a single intravenous or oral administration. The metabolites (M1 and M2) were identified in plasma by UPLC-Q-TOF/MS. The concentrations of the THSG in rat plasma, and bile, urine, or feces samples were determined by HPLC-UV. The results show THSG was rapidly absorbed within 30 min in plasma. Absolute bioavailability of THSG was 40%. Total recovery of unchanged THSG within 24 hr were low (0.041% in bile, 0.06% in feces), whereas the amount of unchanged THSG excreted in the urine within 24 hr was lower than LLOQ.

Keywords:

• 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside
• bioavailability
• metabolism
• pharmacokinetics
• Polygoni multiflori
• UPLC-Q-TOF/MS

ACKNOWLEDGMENT

The author wishes to thank Xu Bai for his expert technical assistance from Waters Technologies (Shanghai) Ltd. This study was supported in part by grants from the National Scientific Foundation of China (Nos. 81001622, 81073029), the project of “As a Major New Drug to Create a Major National Science and Technology Special” (No. 2011ZX09401-308-034) from the Ministry of Science and Technology of the People's Republic of China and the Technology Research Program from Shaanxi Provincial Science and Technology Department (No. 2011K12-69).

Notes

^a C_max: maximum plasma concentration; T_max: time to reach maximum plasma concentration; AUC_(0-t): area under the concentration–time curve from zero up to a definite time t; AUC_(0-∞): area under the concentration–time curve from zero up to infinite time; t _{1/2E phase}: half-life of elimination phase; t _{1/2A phase}: half-life of absorption phase; V_d: volume of distribution; MRT: mean residence time.

^b Data are expressed as mean ± S.D.