title: Quantification of oxyresveratrol analog trans-2,4,3',5'-tetramethoxystilbene in rat plasma by a rapid HPLC method: application in a pre-clinical pharmacokinetic study.
abstract: A rapid HPLC method was developed and validated for the quantification of oxyresveratrol analog trans-2,4,3',5'-tetramethoxystilbene (oxyresveratrol tetramethyl ether, OTE) in rat plasma. Chromatographic separation was achieved on an RP-HPLC column, which was protected by a guard column through a 12 min gradient delivery of a mixture of acetonitrile-water at 50°C. The UV absorbance at 325 nm was recorded. The retention time of OTE and trans-stilbene (internal standard) was about 7.7 and 8.4 min, respectively. The calibration curves were linear (R(2) ≥ 0.9986) with a lower limit of quantification of 15 ng/mL. The intra- and inter-day variations, in terms of RSD, were all lower than 9.8% while the intra-day and inter-day bias ranged from -8.3 to +9.2%. The pharmacokinetics of OTE was assessed in rats using 2-hydroxypropyl-β-cyclodextrin as a dosing vehicle. After intravenous administration, OTE possessed a long terminal elimination half-life (t(1/2) (λz) = 481 ± 137 min) and slow clearance (Cl = 29.1 ± 3.7 mL/min/kg). Upon oral administration, OTE was rapidly absorbed. However, it only displayed minimal plasma exposure and its absolute oral bioavailability (F) was as low as 4.5 ± 3.2%. Fortunately, the levels of OTE after single oral administration were sufficient to inhibit human cytochrome P450 1B1.
authors.affiliation: Department of Pharmacy, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260. phalh@nus.edu.sg
authors.forename: Hai-Shu
authors.initials: HS
authors.lastname: Lin
authors.forename: Qiu-Yi
authors.initials: QY
authors.lastname: Choo
authors.forename: Paul C
authors.initials: PC
authors.lastname: Ho
mesh_terms: D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D008297:Male; D010936:Plant Extracts / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013267:Stilbenes / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: C440850:2,4,3',5'-tetramethoxystilbene; D010936:Plant Extracts; D013267:Stilbenes; C034912:puag-haad