title: A simple and sensitive HPLC-UV method for the quantification of piceatannol analog trans-3,5,3',4'-tetramethoxystilbene in rat plasma and its application for a pre-clinical pharmacokinetic study.
abstract: A simple and sensitive HPLC-UV method was developed and validated for the quantification of piceatannol analog trans-3,5,3',4'-tetramethoxystilbene (M-PIC) in rat plasma. Following protein precipitation with three volumes of acetonitrile, the analytes were separated on a RP-HPLC column, which was protected by a guard column through gradient delivery of a mixture of acetonitrile-water at 40 degrees C. The UV absorbance at 325nm was recorded to quantify M-PIC. The retention time of M-PIC and trans-3,5-dimethoxystilbene (internal standard) was 7.4 and 8.4min, respectively. The calibration curves were linear (R(2)>0.9989) with a lower limit of quantification of 15ng/ml. The intra- and inter-day precisions, in terms of RSD, were all lower than 7.5%. The average analytical recovery ranged from 97.0 to 104.3% while the average absolute recovery ranged from 101.8 to 105.0%. This reliable HPLC method was subsequently applied to assess the pharmacokinetic profile of M-PIC in Sprague-Dawley rats using 2-hydroxypropyl-beta-cyclodextrin as a dosing vehicle. The terminal elimination half-life (t(1/2lambdaz)) and clearance (Cl) of M-PIC were 313+/-20min and 33.1+/-3.9ml/min/kg, respectively; and its absolute oral bioavailability was as high as 50.7+/-15.0%. M-PIC appeared to have a favorable pharmacokinetic profile and further pharmacological investigation on this phyto-stilbene was warranted.
authors.affiliation: Department of Pharmacy, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore. phalh@nus.edu.sg
authors.forename: Hai-Shu
authors.initials: HS
authors.lastname: Lin
authors.forename: Corrado
authors.initials: C
authors.lastname: Tringali
authors.forename: Carmela
authors.initials: C
authors.lastname: Spatafora
authors.forename: Chun
authors.initials: C
authors.lastname: Wu
authors.forename: Paul C
authors.initials: PC
authors.lastname: Ho
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013267:Stilbenes / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene