Pharmacokinetic and Bioavailability Analysis of Etomidate, Metomidate, and Propoxate in Mice Using UPLC-MS/MS

Several studies have reported detection methods for etomidate and its analogues, metomidate and propoxate, but data on their pharmacokinetics and bioavailability are limited. This study develops a UPLC-MS/MS method to simultaneously detect these compounds and evaluates their pharmacokinetics and bioavailability in mice. Plasma samples were processed using methanol-induced protein precipitation. The separation was conducted on a UPLC BEH C18 column with an acetonitrile-water (containing 0.1% formic acid) as mobile phase at a flow rate of 0.4 mL/min, achieving elution within 4 min. Quantitative analysis was performed using MRM mode coupled with ESI in positive ion mode. In this study, mice received etomidate, metomidate, and propoxate via intravenous (1 mg/kg) and oral (10 mg/kg) routes, and the pharmacokinetics were evaluated. The calibration curves demonstrated excellent linearity within the ranges of 0.5-1000 ng/mL for etomidate, 0.504-1080 ng/mL for metomidate, and 0.77-1540 ng/mL for propoxate in mouse plasma, with correlation coefficients (r values) exceeding 0.998. The developed UPLC-MS/MS method was successfully utilized to analyze the pharmacokinetics of etomidate, metomidate, and propoxate. The absolute bioavailability of etomidate, metomidate, and propoxate was determined to be 14.0%, 21.3%, and 15.3%, respectively.