Screening of stabilizers for LC-MS/MS analysis of clevidipine and its primary metabolite in dog whole blood

Background: Clevidipine is an ester-containing antihypertensive agent that undergoes rapid hydrolysis in blood. A reliable stabilizer cocktail containing citric acid and ascorbic acid was established and the LC–MS/MS method was validated for simultaneous determination of clevidipine and its major metabolite in beagle dog whole blood. Results: The stabilizer could nearly completely inhibit the esterase activity. Both analytes were extracted from whole blood by toluene and detected by MS/MS in positive ESI mode. The linearity range was 0.1–100.0 ng/ml for clevidipine and 1.0–1000.0 ng/ml for the primary metabolite. Conclusion: The stabilizer cocktail was able to effectively suppress the activity of esterase in blood. The method was successfully applied to a PK study of clevidipine in beagle dogs.