Abstract: In order to find an effective way to test the micro oil leakage and judge the end point of sublimation drying during the biochemical medicine vacuum freeze-drying process, the leakage of silicone oil in the lyophilizer and primary sublimation drying process online were monitored by mass spectrometer. The results showed that the original silicone oil quantity was 1×10^-12 in the freeze-drying chamber tested by mass spectrometer. The mass spectrometer could test the leakage of silicone oil when the concentration was 1×10^-6 in 15 minutes. With the lyophilizer no-load running, N₂、O₂、H₂O、and Ar gas accounted for 82.31%、15.68%、1.37%、0.64% respectively. In the late period of medicine primary sublimation drying process, the four gases accounted for 82.47%、14.9%、1.75%、0.88% respectively. Each gas can be used to judge the end of the medicine sublimation drying progress in a no-load freeze-drying chamber. The present study provides a new method for the judgement of silicone oil leakage and biochemical medicine primary freeze-drying progress.

Key words: freeze-drying process, mass spectrometer, biochemical medicine, silicone oil

摘要： 为了探索检测生化药品真空冷冻干燥过程中冻干室内发生微量漏油和判断升华干燥结束点的有效方法，采用质谱仪对冻干机内硅油泄漏和一次升华干燥过程进行在线监测。结果表明，质谱仪能检测到冻干室内本底硅油量为1×10^-12，当硅油泄漏量为1×10^-6时，采用质谱仪可在15min内检测到；当冻干机空载运行时，采用质谱仪检测N₂、O₂、H₂O、Ar占气体体积分数分别为82.31%、15.68%、1.37%、0.64%，药品在一次升华干燥过程后期，4种气体占气体体积分数分别为82.47%、14.9%、1.75%、0.88%，可用空载冻干室内空气各组分所占比重判断药品一次升华干燥过程的结束。本研究为冻干机内硅油泄漏和生化药品冻干进程的判断提供了新方法。

关键词: 冻干过程, 质谱仪, 生化药品, 硅油