Determination of etomidate concentration in plasma of beagle dogs by LC-MS/MS and its application in bioequivalence evaluation
OBJECTIVE To establish a liquid chromatography-mass spectrometry(LC-MS/MS)method for the determina-tion of etomidate in plasma of Beagle dogs and apply to bioequivalence evaluation of two etomidate medium/long chain fat emul-sion injection.METHODS LC-MS/MS analysis method was established to detect the content of etomidate in Beagle dog plasma.Twelve Beagle dogs were designed with a dual cycle,double crossover design and intravenous injection of 0.52 mg·kg-1 etomidate medium/long chain fat emulsion injection.Pharmacokinetics were evaluated.RESULTS The linear range in Beagle dog plasma was 1-200 ng·mL-1.The extraction recovery rates were low,medium,and high concentrations were 97.4％,100.3％,and 97.1％,respectively.The precision and accuracy deviation range between batches/within batches was-5.2％-6.1％,and the coefficient of variation was 6.5％.All meet the requirements for analysis and detection.The AUC0-10 h values for the test and reference formulation were(171.0±27.1)and(176.0±25.3)μg·h·L-1 respectively,Cmax were(398.0±59.5),(413.0±100.0)μg·L1,there was no statistical difference between the two.CONCLUSION This article establishes a simple,sensitive,and accurate LC-MS/MS method for the determination of etomidate in plasma.After intravenous injection of 0.52 mg· kg-1 etomidate medium/long chain fat emulsion injection into Beagle dogs,there was no statistically significant difference in the AUC0-10h and Cmax of etomidate between the test and reference formulation in Beagle dog plasma,indicating bioequivalence.
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万方数据
维普
