Sensitive analysis and pharmacokinetic study of epalrestat in C57BL/6J mice

Epalrestat is clinically applied for the management of diabetic peripheral neuropathy, yet its pharmacokinetic properties are not well understood. In this study, a rapid and sensitive LC–MS/MS method was established for assaying epalrestat in bio-samples of mice. The method was validated and it showed a good linearity over the range of 2–5000 ng/mL, a precision of less than 12.3%, and recovery and matrix effects of 112.5–123.6% and 87.9–89.5%, respectively. After administration of a single dose of epalrestat administered, the exposure level of AUC_0–∞ was positively dose-dependent and the mean C_max, AUC_0–12 h, T_1/2, and MRT were 36.23 ± 7.39 μg/mL, 29,086.5 μg/L h, 1.2 h and 1.8 h, respectively. Epalrestat was highly exposed in stomach, intestine, liver and kidney, and only a small amount was detected in brain, urine and feces. Multi-dose of epalrestat significantly increased MRT and apparent volume of distribution (V_d) relative to those of a single-dose.