LC-MS/MS测定Beagle犬血浆中依托咪酯浓度及其在生物等效性评价中的应用  

Determination of etomidate concentration in plasma of beagle dogs by LC-MS/MS and its application in bioequivalence evaluation

作　　者：刘静欢 侯海婷 左亚茹 马晓阳 孙立杰[1,3,4] 杨娴 LIU Jinghuan;HOU Haiting;ZUO Yaru;MA Xiaoyang;SUN Lijie(Pharmaceutical Research Institute of Shijiazhuang No.4 Pharmaceutical Co.,Ltd.,Hebei Shijiazhuang 050000,China;College of Pharmacy,Hebei Medical University Hebei Shijiazhuang 050000,China;Industrial Technology Research Insti-tute of Chemical Sterile Preparations Shijiazhuang,Hebei Shijiazhuang 050000,China;Postdoctoral Research Workstation of Shijiazhuang No.4 Pharmaceutical Co.,Ltd.-Hebei Medical University Joint Postdoctoral Research Station,Hebei Shijia-zhuang 050000,China)

机构地区：[1]石家庄四药有限公司研发中心,河北石家庄050000 [2]河北医科大学药学院,河北石家庄050000 [3]化学药品无菌制剂产业技术研究院,河北石家庄050000 [4]河北省大容量注射剂工程技术研究中心,河北石家庄050000 [5]石家庄四药有限公司-河北医科大学联合博士后科研工作站,河北石家庄050000

出　　处：《中国医院药学杂志》2024年第2期186-190,共5页Chinese Journal of Hospital Pharmacy

基　　金：河北省创新能力提升计划项目(编号:225A2704D);河北省高层次人才资助项目(编号:B2022003038)。

摘　　要：目的:建立液相色谱-质谱联用(LC-MS/MS)分析方法测定Beagle犬血浆中依托咪酯的浓度,并考察2种依托咪酯中/长链脂肪乳注射液的生物等效性。方法:建立LC-MS/MS分析方法检测Beagle犬血浆中依托咪酯含量。12只Beagle犬采用双周期双交叉设计,静脉注射依托咪酯中/长链脂肪乳注射液0.52 mg·kg^(-1),检测血浆中依托咪酯的含量,计算药动学参数。结果:Beagle犬血浆中的线性范围为1~200 ng·mL^(-1)。低中高浓度提取回收率分别为97.4%、100.3%和97.1%,批间/批内精密度和准确度偏差范围在-5.2%~6.1%,变异系数6.5%,均满足分析检测要求。受试制剂与参比制剂AUC0-10 h分别为(171.0±27.1),(176.0±25.3)μg·h·L^(-1),Cmax分别为(398.0±59.5),(413.0±100.0)μg·L^(-1),两者无统计学差异。结论:建立的LC-MS/MS测定方法简便、灵敏、准确,可用于检测血浆中依托咪酯的含量。Beagle犬静脉注射0.52 mg·kg^(-1)依托咪酯中/长链脂肪乳注射液后,受试制剂与参比制剂在Beagle犬血浆中依托咪酯的AUC0~10 h和Cmax无统计学差异,表现出生物等效性。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·L^(-1),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 AUC0-10 h and Cmax of etomidate between the test and reference formulation in Beagle dog plasma,indicating bioequivalence.

关 键 词：依托咪酯 血浆 液相色谱-质谱联用 BEAGLE犬 

分 类 号：R917[医药卫生—药物分析学]