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.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.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.
