A simple HPLC method was established to quantify trans-3,4,5,4'-tetramethoxystilbene (MR-4 or DMU-212) in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column through an 11 min gradient delivery of a mixture of acetonitrile and water at a flow rate of 1.5 mL/min at 50 degrees C. The limit of quantification was 15 ng/mL. The intra- and interday precisions in terms of relative standard deviation were <9% at all concentrations. Similarly, the accuracy was good, and the bias rates ranged within +/- 7%. The pharmacokinetic profiles of MR-4 were subsequently assessed in rats using 2-hydroxypropyl-beta-cyclodextrin as a dosing vehicle. Upon intravenous administration, MR-4 displayed moderate clearance (46.5 +/- 7.6 mL/min/kg) and terminal elimination half-life (154 +/- 80 mm). However, the absolute oral bioavailability of MR-4 was low (6.31 +/- 3.30%). Future investigation on MR-4 as a chemotherapeutic agent should be focused on colorectal cancers.
Quantification of trans-3,4,5,4 '-Tetramethoxystilbene in Rat Plasma by HPLC: Application to Pharmacokinetic Study RID G-2581-2010
TRINGALI, Corrado;
2011-01-01
Abstract
A simple HPLC method was established to quantify trans-3,4,5,4'-tetramethoxystilbene (MR-4 or DMU-212) in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column through an 11 min gradient delivery of a mixture of acetonitrile and water at a flow rate of 1.5 mL/min at 50 degrees C. The limit of quantification was 15 ng/mL. The intra- and interday precisions in terms of relative standard deviation were <9% at all concentrations. Similarly, the accuracy was good, and the bias rates ranged within +/- 7%. The pharmacokinetic profiles of MR-4 were subsequently assessed in rats using 2-hydroxypropyl-beta-cyclodextrin as a dosing vehicle. Upon intravenous administration, MR-4 displayed moderate clearance (46.5 +/- 7.6 mL/min/kg) and terminal elimination half-life (154 +/- 80 mm). However, the absolute oral bioavailability of MR-4 was low (6.31 +/- 3.30%). Future investigation on MR-4 as a chemotherapeutic agent should be focused on colorectal cancers.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
