Determination of trans-2,4,3',4',5'-pentamethoxystilbene in rat plasma and its application to pharmacokinetic study

trans-2,4,3',4',5'-Pentamethoxystilbene (2,4,3',4',5'-PMS) is a resveratrol derivative that displayedpromising pre-clinical anti-cancer activities. In this study, a simple HPLC method was developed andvalidated to determine 2,4,3',4',5'-PMS in rat plasma. The lower limit of quantification was 9 ng/ml. Theintra- and inter-day precision in terms of relative standard deviation was less than 9.7% and the biasrate ranged from−6.4 to +7.8%. The pharmacokinetics of 2,4,3',4',5'-PMS was subsequently studied inSprague-Dawley rats. Upon intravenous administration (0.75 mg/kg), 2,4,3',4',5'-PMS displayed moderateclearance (58.5±19.5 ml/min/kg) and terminal elimination half-life (147±61 min). Aqueous solubilityappeared to be a barrier to oral absorption. When suspension was given (4 mg/kg), the absolute oralbioavailability was almost nil; when 2,4,3',4',5'-PMS was fully solubilized by randomly methylated-beta-cyclodextrin, it possessed a low bioavailability (3.63±2.06%). The pharmacokinetic comparison among2,4,3',4',5'-PMS and other methoxylated stilbenes suggested that the 2-methoxy group was unfavorableto oral bioavailability. Future investigations on 2,4,3',4',5'-PMS should be focused on chemo-preventionof colorectal carcinogenesis.