Determination of Z-3,5,4'-trimethoxystilbene in rat plasma by a simple HPLC method: Application in a pre-clinical pharmacokinetic study

Abstract

A simple HPLC method had been developed and validated to quantify Z-3,5,4'-trimethoxystilbene (Z-TMS), a phyto-stilbene with potent anti-cancer activities in rat plasma. Chromatographic separation was achieved on a reversed phase-HPLC column, which was protected by a guard column through a 13.5-min gradient delivery of a mixture of acetonitrile and water at a flow rate of 1.5ml/min at 50°C. The UV absorbance at 300nm was recorded. Z-TMS and E-stilbene (internal standard) eluted at 8.8 and 9.3min, respectively. The calibration curve was linear within the range of 33-2500ng/ml (R2>0.9995) and 10ng/ml was the lower limit of detection. The intra- and inter-day precisions were good and the relative standard deviation was all lower than 10%. The analytical recovery of Z-TMS in plasma ranged from 94.6±9.1% to 97.0±2.1%. This HPLC method was successfully applied to assess the pharmacokinetic profile of Z-TMS in Sprague-Dawley rats using hydroxypropyl-β-cyclodextrin (HP-β-CyD) as a dosing vehicle. Although Z-TMS displayed negligible oral bioavailability, it had a fairly long terminal elimination half-life, abundant plasma drug exposure and limited clearance following intravenous administration. As Z-TMS had favorable intravenous pharmacokinetic profile, further investigation on its potential as a cancer chemotherapeutic agent is warranted. © 2010 Elsevier B.V..