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 9 ng/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 (0.75 mg/kg), 2,4,3',4',5'-PMS displayed moderate clearance (58.5 ± 19.5 ml/min/kg) and terminal elimination half-life (147 ± 61 min). Aqueous solubility appeared to be a barrier to oral absorption. When suspension was given (4 mg/kg), the absolute oral bioavailability 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 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.
Determination of trans-2,4,3',4',5'-pentamethoxystilbene in rat plasma and its application to pharmacokinetic study
TRINGALI, Corrado;
2012-01-01
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 9 ng/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 (0.75 mg/kg), 2,4,3',4',5'-PMS displayed moderate clearance (58.5 ± 19.5 ml/min/kg) and terminal elimination half-life (147 ± 61 min). Aqueous solubility appeared to be a barrier to oral absorption. When suspension was given (4 mg/kg), the absolute oral bioavailability 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 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
