气相色谱—串联质谱法测定阿哌沙班中2-氯乙酰乙酸乙酯的残留量  

Determination of Genotoxic Impurity 2-chloroacetoacetic Acid Ethyl Ester in Apixaban by GC-MS/MS

作　　者：卢忠秋 王玉如 刘晓敏 徐淑媛 穆双双 兰公剑 Lu Zhongqiu;Wang Yuru;Liu Xiaomin;Xu Shuyuan;Mu Shuangshuang;Lan Gongjian(Nanjing Chia-Tai Tianqing Pharmaceutical Co.,Ltd.,Nanjing 210046,China)

机构地区：[1]南京正大天晴制药有限公司,江苏南京210046

出　　处：《山东化工》2024年第9期136-138,共3页Shandong Chemical Industry

摘　　要：目的:建立一种气相色谱—串联质谱(GC-MS/MS)方法,用于测定阿哌沙班中潜在基因毒性杂质2-氯乙酰乙酸乙酯的残留量。方法:用聚乙二醇[VF-WAXms(30 mm×0.25 mm×0.25μm)]为固定液的毛细管色谱柱;进样口温度为230℃;流速1.0 mL/min;载气:氦气;不分流进样。采用电子轰击离子源(EI),选择离子监测模式(SIM)。结果:2-氯乙酰乙酸乙酯在0.05~1.02μg/mL质量浓度范围内呈现良好的线性关系(r=0.9985);定量限浓度是0.02μg/mL;检出限是0.01μg/mL;三份不同浓度水平的平均回收率为97.9%(RSD=4.2%)。结论:所建立的GC-MS/MS测定方法灵敏度高、专属性强和准确度好,可用于阿哌沙班中2-氯乙酰乙酸乙酯的测定。Objective:To establish a gas chromatography-mass spectrometry(GC-MS/MS)method for the determination of genotoxic impurities 2-chloroacetoacetic acid ethyl ester in Apixaban.Methods:The sample was performed on[VF-WAXms(30 mm×0.25 mm×0.25μm)]capillary column(polyethylene glycol as fixed liquid),the inlet temperature was 230℃.The carrier gas flow rate was set at 1.0 mL/min with splitless injection.The carrier gas was Helium.It was detected by selected ion monitoring(SIM)mode with electron impact ion source.Results:The calibration curve of 2-chloroacetoacetic acid ethyl ester was in a good linearity over the range of 0.05~1.02μg/mL(r=0.9985)the limit of quantification was 0.02μg/mL,the detection limit was 0.01μg/mL.The average spiked recovery was 97.9%and RSD was 4.2%.Conclusion:This method has the advantage of good sensitivity,high specificity and high precision,which can be used for the determination of 2-chloroacetoacetic acid ethyl ester in apixaban.

关 键 词：阿哌沙班 基因毒性杂质 2-氯乙酰乙酸乙酯 气相色谱—串联质谱 

分 类 号：O657.63[理学—分析化学]