LC-MS/MS method for the quantification of aldose reductase inhibitor-epalrestat and application to pharmacokinetic study.

A simple and rapid LC-MS/MS method was developed and validated for the quantification of epalrestat, an aldose reductase inhibitor for the treatment of diabetic neuropathy. Following protein precipitation epalrestat and IS were eluted with 10mM ammonium acetate and acetonitrile using a rapid gradient program on reverse phase column. Multiple reaction monitoring mode was used to monitor the transitions of m/z 318→58 for epalrestat and m/z 410→348 for the IS. The assay exhibited a linear dynamic range of 2-5,000 ng/mL for epalrestat in rat plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The within batch accuracy was in the range of 101.3-108.0% with precision in the range of 3.0-12.3%. All the other validation parameters were within the acceptable limits. Validated method was applied to analyze rat plasma samples obtained from a pharmacokinetic study. After oral administration of epalrestat at 10mg/kg to wistar rats (n=3) mean C(max), AUC(0-24) (ngh/mL) and t(1/2) were found to be 4077 ± 1327 ng/mL, 8989 ± 1590 ngh/mL and 2.9 ± 1.4h, respectively. Bioavailability was found to be 90 ± 14% for epalrestat in male wistar rats.