title: Determination of minalrestat (an aldose reductase inhibitor) in rat, dog and human plasma by high-performance liquid chromatography.
abstract: A high-performance liquid chromatographic (HPLC) method was developed for the quantification of minalrestat (a potent aldose reductase inhibitor) in rat, dog and human plasma. Minalrestat and internal standard (I.S.) were extracted from plasma by either solid-phase extraction (SPE) or liquid-liquid extraction (human plasma). Plasma extracts were chromatographed on a Hypersil ODS column with 3-microm packing with a mobile phase of acetonitrile-0.05 M potassium phosphate buffer, pH 3.0 (45:55, v/v) at 0.2 ml/min. The signal in the eluent was enhanced by UV-irradiation when passing through a photochemical reaction unit with a 10-m reaction coil, prior to detection by UV absorbance at 255 nm. The intra-day coefficients of variation was less than 9% in rat, dog and human plasma and the intra-day accuracy (%MRE) was within +/-5% in all matrices tested. The inter-day coefficients of variation were less than 12% in rat and human plasma and the accuracy (%MRE) was within +/-15%. Minalrestat was stable for at least 60 days in rat and human plasma and at least 30 days in dog plasma samples stored at -20 degrees C. In human plasma samples, the analyte was stable for up to 5 cycles of freezing and thawing. This method has been applied successfully for the evaluation of the pharmacokinetics of minalrestat in rats, dogs and humans.
authors.affiliation: Bioanalytical R&D/Division of Drug Metabolism, Wyeth-Ayerst Research, Pearl River, NY 10965, USA.
authors.forename: S Y
authors.initials: SY
authors.lastname: Tse
authors.forename: R
authors.initials: R
authors.lastname: Whetsel
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013045:Species Specificity
chemical_list: D004791:Enzyme Inhibitors; C091470:WAY 121-509; D000449:Aldehyde Reductase