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

Area of Science:

• Pharmacology
• Analytical Chemistry

Background:

• Limited pharmacokinetic and bioavailability data exist for etomidate and its analogues, metomidate and propoxate.
• Accurate detection methods are crucial for understanding drug behavior in vivo.

Purpose of the Study:

• To develop and validate a UPLC-MS/MS method for simultaneous detection of etomidate, metomidate, and propoxate.
• To evaluate the pharmacokinetics and absolute bioavailability of these compounds in mice.

Main Methods:

• Development of a UPLC-MS/MS method using methanol-induced protein precipitation and a BEH C18 column.
• Analysis of plasma samples using ESI in positive ion mode and MRM.
• Administration of compounds via intravenous and oral routes in mice.

Main Results:

• The UPLC-MS/MS method demonstrated excellent linearity (r > 0.998) and sensitivity for all three compounds.
• Pharmacokinetic parameters were successfully evaluated in mice.
• Absolute bioavailability was determined as 14.0% for etomidate, 21.3% for metomidate, and 15.3% for propoxate.

Conclusions:

• A validated UPLC-MS/MS method enables simultaneous quantification of etomidate, metomidate, and propoxate in mouse plasma.
• The study provides crucial pharmacokinetic and bioavailability data for these etomidate analogues in a preclinical model.