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

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2017-06, Vol.1055-1056, p.98-103
• Main Authors: Huang, Jingqiu, Sun, Runbin, Feng, Siqi, He, Jun, Fei, Fei, Gao, Haoxue, Zhao, Yuqing, Zhang, Yue, Gu, Huilin, Aa, Jiye, Wang, Guangji
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Chromatography, High Pressure Liquid - methods; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - blood; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - urine; Epalrestat; Excretion; Female; LC–MS/MS; Limit of Detection; Male; Mice, Inbred C57BL; Pharmacokinetics; Rhodanine - administration & dosage; Rhodanine - analogs & derivatives; Rhodanine - blood; Rhodanine - pharmacokinetics; Rhodanine - urine; Spectrometry, Mass, Electrospray Ionization - methods; Thiazolidines - administration & dosage; Thiazolidines - blood; Thiazolidines - pharmacokinetics; Thiazolidines - urine; Tissue Distribution
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2017.03.040

•A sensitive LC–MS/MS method was established for assaying epalrestat in bio-samples.•Pharmacokinetic properties of epalrestat were evaluated in mice.•Epalrestat was highly exposed in stomach, intestine, liver and kidney.•The exposure level of AUC0–∞ was linearly dependent on the dosages of epalrestat.•Multi-dose of epalrestat increased MRT and Vd relative to single-dose. 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 2–5000ng/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 AUC0–∞ was positively dose-dependent and the mean Cmax, AUC0–12h, T1/2, and MRT were 36.23±7.39μg/mL, 29,086.5μg/Lh, 1.2h and 1.8h, 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 (Vd) relative to those of a single-dose.