Quantification of oxyresveratrol analog trans-2,4,3',5'-tetramethoxystilbene in rat plasma by a rapid HPLC method: application in a pre-clinical pharmacokinetic study

A rapid HPLC method was developed and validated for the quantification of oxyresveratrol analog trans‐2,4,3′,5′‐tetramethoxystilbene (oxyresveratrol tetramethyl ether, OTE) in rat plasma. Chromatographic separation was achieved on an RP‐HPLC column, which was protected by a guard column through a 12 min gradient delivery of a mixture of acetonitrile–water at 50°C. The UV absorbance at 325 nm was recorded. The retention time of OTE and trans‐stilbene (internal standard) was about 7.7 and 8.4 min, respectively. The calibration curves were linear (R² ≥ 0.9986) with a lower limit of quantification of 15 ng/mL. The intra‐ and inter‐day variations, in terms of RSD, were all lower than 9.8% while the intra‐day and inter‐day bias ranged from ?8.3 to +9.2%. The pharmacokinetics of OTE was assessed in rats using 2‐hydroxypropyl‐β‐cyclodextrin as a dosing vehicle. After intravenous administration, OTE possessed a long terminal elimination half‐life (t_{1/2 λz} = 481 ± 137 min) and slow clearance (Cl = 29.1 ± 3.7 mL/min/kg). Upon oral administration, OTE was rapidly absorbed. However, it only displayed minimal plasma exposure and its absolute oral bioavailability (F) was as low as 4.5 ± 3.2%. Fortunately, the levels of OTE after single oral administration were sufficient to inhibit human cytochrome P450 1B1. Copyright © 2010 John Wiley & Sons, Ltd.