毛细管柱顶空气相色谱法测定培美曲赛二钠中有机溶剂残留量

Determination of Residual Organic Solvents in Pemetrexed Disodium by Headspace-Gas Chromatography

目的建立以外标法测定培美曲塞二钠中溶剂残留量的顶空气相色谱法,可同时测定该化合物中正己烷、丙酮、四氢呋喃、乙酸乙酯、甲醇、二氯甲烷、乙醇、乙腈、N,N-二甲基甲酰胺9种有机溶剂的残留量。方法以交联聚乙二醇为固定相的毛细管柱,氢火焰离子检测器,顶空进样方式,柱温起始温度为40℃,保持10 min,然后以每分钟10℃的速率升至120℃,保持2 min。结果正己烷、丙酮、四氢呋喃、乙酸乙酯、甲醇、二氯甲烷、乙醇、乙腈、N,N-二甲基甲酰胺9种溶剂分离良好,线性范围分别为2.98～59.60μg/mL(r=0.9990),50.21～1 004.20μg/mL(r=0.999 9),50.33～1 006.60μg/mL(r=0.999 5),50.17～1 003.40μg/mL(r=0.999 4),30.11～602.20μg/mL(r=0.999 9),6.11～122.20μg/mL(r=0.998 8),50.33～1 006.60μg/mL(r=0.999 8),4.15～83.00μg/mL(r=0.999 5),8.74～174.80μg/mL(r=0.999 2);最低检测浓度分别为5.8,2.5,2.0,2.0,3.0,6.0,2.0,1.6,8.9μg/mL;9种溶剂的回收率良好。结论所用方法简便、灵敏、准确,适用于培美曲塞二钠有机残留量的测定。

Objective To establish a headspace-GC method for quantification of residual organic solvents in pemetrexed disodium.Methods The GC condition was consisted of a ECTM-Wax（30 m×0.53 mm×1.20 μm） capillary column,column temperature was maintained at 40 ℃for 10 min,then increased to 120 ℃at 10 ℃/min,and at 120 ℃for 2 min.Results All of 9 solvents were separated and good linear responses were obtained in the following range,n-hexane 2.98～59.60 μg/mL（r=0.999 0）,acetone 50.21-1 004.20 μg/mL（r=0.999 9）,tetrahydrofuran 50.33-1 006.60 μg/mL（r=0.999 5）,ethyl acetate 50.17-1 003.40 μg/mL（r=0.999 4）,methanol 30.11-602.20 μg/mL（r=0.999 9）,dichloromethane 6.11-122.20 μg/mL（r=0.998 8）,ethanol 50.33-1 006.60 μg/mL（r=0.999 2）,acetonitrile 4.15-83.00 μg/mL（r=0.999 5） and N,N-dimethylforamide 8.74-174.80 μg/mL（r=0.999 2） respectively;the recovery rate of 9 solvents were good;the limit of detection（LOD） of 5.8,2.5,2.0,2.0,3.0,6.0,2.0,1.6,8.9 μg/mL,respectively.Conclusion This rapid,simple and accurate GC method is useful for quality control of residual organic volatiles in Pemetrexed disodium.