顶空气相色谱法测定美罗培南中有机溶剂的残留量

Determination of Residual Organic Solvents in Meropenem by Headspace Gas Chromatography

目的:建立以顶空气相色谱法同时测定美罗培南中有机溶剂甲醇、乙醇、丙酮、乙腈、二氯甲烷、正丁醇残留量的方法。方法:色谱柱为DB-624石英毛细管柱,柱温采用程序升温,检测器为氢火焰离子化检测器,检测器温度为250℃,进样口温度为200℃,载气为氮气,水为溶剂。结果:甲醇、乙醇、丙酮、乙腈、二氯甲烷、正丁醇的检测浓度的线性范围分别为12～600(r=0.9998)、20～1000(r=0.9999)、20～1000(r=0.9999)、1.64～82(r=0.9998)、2.4～120(r=0.9996)、20～1000μg·mL-(1r=0.9999);平均回收率为98.8%～99.6%;RSD分别为1.0%、2.2%、0.9%、2.2%、1.6%、1.1%;最低检出限为0.06～0.43ng;3批样品中6种有机溶剂残留量均符合2005年版《中国药典》中的相关规定。结论:本方法简单、准确、灵敏度高、重复性好,可用于美罗培南中有机溶剂残留量的测定。

OBJECTIVE： To develop a headspace GC method for determination of residual organic solvents invovling methanol, alcohol, acetone, acetonitrile, dichloromethane and n-butanol in meropenem. METHODS： The residual organic solvents were separated on DB-624 capillary column using temperature programming. FID was used as detector with a temperature of 250 ℃ with nitrogen as cartier gas and water as solvent. The inlet temperature was 200 ℃. RESULTS： The linear range were 12-600 μg·mL^-1 （r=0.999 8） for methanol, 20-1 000μg·mL^-1 （r=0.999 9） for alcohol, 20-1 000μg·mL^-1 （r=0.999 9） for acetone, 1.64-82μg·mL^-1（r=0.999 8） for acetonitrile, 2.4-120 μg·mL^-1（r=0.999 6） for dichloromethane and 20-1 000 μg·mL^-1 （r= 0.999 9） for n-butanol with RSD of 1.0%, 2.2%, 0.9%, 2.2%, 1.6%, 1.1%, respectively. The average recoveries were ranged from 98.8% to 99.6%. The LOD were about 0.06-0.43 ng. The residual levels of six organic solvents in 3 batches samples were all up to the standard stated in Chinese Pharmacopeia （2005 edition）. CONCLUSION： The method is simple, accurate, sensitive and reproducible for determination of residual organic solvents in meropenem.