| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1214008 | Journal of Chromatography B | 2012 | 5 Pages |
WJ-38 is an aldose reductase inhibitor that is being developed for the treatment of diabetic complications. The present paper describes a sensitive and specific liquid chromatography-tandem mass spectrometry method for the determination of WJ-38 in rat plasma. Partial denaturation of plasma proteins with methanol followed by liquid–liquid extraction using ethyl acetate was used to extract strongly protein-bound WJ-38 from rat plasma. Chromatographic separation was performed on an Inertsil ODS-3 column with an isocratic mobile phase consisting of acetonitrile, water and formic acid (75:25:0.125, v/v/v). Mass spectrometric detection was achieved by a triple-quadrupole mass spectrometer equipped with an ESI interface operating in positive ionization mode. Quantitation was performed using selected reaction monitoring of precursor-product ion transitions at m/z 392 → 246 for WJ-38 and m/z 446 → 321 for glipizide (internal standard). A linear calibration curve was obtained over the concentration range of 10.0–10,000 ng/mL for WJ-38 in rat plasma. The intra- and inter-day precisions were less than 13.6% and the accuracy was within ±5.3%. The extraction recovery of WJ-38 from rat plasma was over 66.0%. The validated method has been successfully applied to a pharmacokinetic study in rats after intragastrical administration of WJ-38.
► WJ-38 is a potent aldose reductase inhibitor for diabetic complications. ► It is a strongly protein-bound compound (over 97% was bound to plasma proteins). ► A sensitive and specific LC–MS/MS method was developed for WJ-38 analysis. ► Special emphasis was focused on the effective extraction of WJ-38 from rat plasma. ► The chromatographic run time was 3.5 min and the LLOQ was 10.0 ng/mL.
