title: Determination of trans-2,4,3',4',5'-pentamethoxystilbene in rat plasma and its application to a pharmacokinetic study.
abstract: trans-2,4,3',4',5'-Pentamethoxystilbene (2,4,3',4',5'-PMS) is a resveratrol derivative that displayed promising pre-clinical anti-cancer activities. In this study, a simple HPLC method was developed and validated to determine 2,4,3',4',5'-PMS in rat plasma. The lower limit of quantification was 9ng/ml. The intra- and inter-day precision in terms of relative standard deviation was less than 9.7% and the bias rate ranged from -6.4 to +7.8%. The pharmacokinetics of 2,4,3',4',5'-PMS was subsequently studied in Sprague-Dawley rats. Upon intravenous administration (0.75mg/kg), 2,4,3',4',5'-PMS displayed moderate clearance (58.5±19.5ml/min/kg) and terminal elimination half-life (147±61min). Aqueous solubility appeared to be a barrier to oral absorption. When suspension was given (4mg/kg), the absolute oral bioavailability was almost nil; when 2,4,3',4',5'-PMS was fully solubilized by randomly methylated-β-cyclodextrin, it possessed a low bioavailability (3.63±2.06%). The pharmacokinetic comparison among 2,4,3',4',5'-PMS and other methoxylated stilbenes suggested that the 2-methoxy group was unfavorable to oral bioavailability. Future investigations on 2,4,3',4',5'-PMS should be focused on chemo-prevention of colorectal carcinogenesis.
authors: Department of Pharmacy, National University of Singapore, 10 Kent Ridge Crescent, Singapore. phalh@nus.edu.sg
authors: Hai-Shu
authors: HS
authors: Lin
authors: Carmela
authors: C
authors: Spatafora
authors: Corrado
authors: C
authors: Tringali
authors: Paul C
authors: PC
authors: Ho
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D057230:Limit of Detection; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D012995:Solubility; D013267:Stilbenes / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: C544677:2,3',4,4',5'-pentamethoxystilbene; D013267:Stilbenes