培美曲塞二钠原料药中4种残留溶剂的测定

Determination of Four Residual Solvents in Pemetrexed Disodium

目的:建立并优化了培美曲塞二钠中二氯甲烷、乙醇、丙酮、N,N-二甲基甲酰胺4种残留溶剂的测定方法。方法:采用DB-624柱,FID检测器,程序升温,顶空进样法测定二氯甲烷的残留量;直接进样法测定乙醇、丙酮、N,N-二甲基甲酰胺的残留量。结果:二氯甲烷、乙醇、丙酮和N,N-二甲基甲酰胺的线性范围分别为3.1~61.7μg/mL(r=0.9994)、25.4~507.7μg/mL(r=0.9992)、24.1~481.8μg/mL(r=0.9998);4.6~91.2μg/mL(r=0.9992);回收率分别为99.7%、101.2%、100.6%、99.3%;精密度RSD分别为2.4%、1.7%、1.3%、2.8%(n=6);检测限分别为0.3、2.0、1.4、0.5μg/mL。结论:该方法快速、灵敏、准确,可作为培美曲塞二钠中残留溶剂的测定方法。

Objective:To establish a method for the determination of residual solvents of dichloromethane,ethanol,acetone,N,N-dimethylformamide in pemetrexed disodium.Methods:By using DB-624 column,FID detector,temperature programming method,the residual amounts of dichloromethane was determined by headspace sampling method and the residual amounts of ethanol,acetone,N,N-dimethylformamide were determined by direct injection method.Results:The standard curves were linear in the range of 3.1~61.7μg/mL(r=0.9994)for dichloromethane,25.4~507.7μg/mL(r=0.9992)for ethanol,24.1~481.8μg/mL(r=0.9998)for acetone and 4.6~91.2μg/mL(r=0.9992)for N,N-dimethylformamide.The recovery rates were 99.7%,101.2%,100.6% and 99.3% with precision RSD of 2.4%,1.7%,1.3% and 2.8%(n=6).Detection limits were 0.3,2.0,1.4,0.5μg/mL,respectively.Conclusion:This method is rapid,sensitive and accurate,so as to be used for the determination of residual solvents in penetrexed disodium.