GC-MS法同时测定阿糖胞苷中氯甲烷、氯乙烷和2-氯丙烷的残留量  

Simutaneous Determination of Methychloride、Ethylchloride and 2-Chloropropane in Cytarabine by GC-MS

作　　者：张欣娜 邢倩斌 栗伟娜 牛亚蒙 梁敏 ZHANG Xinna;XING Qianbin;LI Weina;NIU Yameng;LIANG Min(CSPC ZhongQi Pharmaceutical Technology(Shijiazhuang),ChinaState Key Laboratory of Novel Pharmaceutical Preparation and Excipients,Shijiazhuang 050035,China)

机构地区：[1]石药集团中奇制药技术(石家庄)有限公司新型药物制剂与辅料国家重点实验室,河北石家庄050035

出　　处：《广州化学》2024年第3期70-73,I0004,共5页Guangzhou Chemistry

摘　　要：建立了气相色谱-质谱联用法(GC-MS)测定阿糖胞苷原料中潜在基因毒性杂质氯甲烷、氯乙烷和2-氯丙烷。采用的色谱柱为TRACETM TR-V1毛细管柱(60 m×0.25 mm,1.4μm),采用程序升温方式,在选择性离子检测(SIM)模式下,氯甲烷m/z为50,氯乙烷m/z为64,2-氯丙烷m/z为78,采用外标法进行定量。载气为氦气,顶空瓶平衡温度60℃,平衡时间30min,进样口温度100℃,分流进样,分流比4∶1。结果表明,氯甲烷、氯乙烷和2-氯丙烷分别在125~1000、125~1000和128~1025 ng/mL范围内线性关系良好(r≥0.999),检测限分别为37.5、37.5和38.4 ng/mL,定量限分别为125、125和128 ng/mL,回收率均在90.8%~104.8%范围内。建立的GC-MS测定方法专属、准确、灵敏,可用于阿糖胞苷原料药中氯甲烷、氯乙烷和2-氯丙烷残留量的同时测定。A gas chromatography-mass spectrometry(GC-MS)method was established for the determination of potentially genotoxic impurities such as chloromethane,chloroethane and 2-chloropropane in cytarabine raw materials.TRACETM TR-V1 capillary column(60 m×0.25 mm,1.4μm)was used.Adopt programmed temperature rise mode,in the mode of selective ion detection(SIM),the m/z of chloromethane was 50,the m/z of chloroethane was 64,and the m/z of 2-chloropropane was 78.The external standard method was used for quantification.The carrier gas is helium,the equilibrium temperature of the headspace bottle is 60℃,the equilibrium time is 30 min,the temperature of the injection port is 100℃,and the split injection is carried out with a split ratio of 4∶1.The results showed that the linear relationships of chloromethane,chloroethane and 2-chloropropane were good in the ranges of 125~1000 ng/mL,125~1000 ng/mL and 128~1025 ng/mL,respectively(r≥0.999).The detection limits were 37.5,37.5 and 38.4 ng/mL,respectively.The quantitative limits were 125,125 and 128 ng/mL,respectively.The recovery rates are all in the range of 90.8%~104.8%.The established GC-MS method is exclusive,accurate and sensitive,and can be used for the determination of chloromethane,chloroethane and 2-chloropropane residues in cytarabine raw materials.

关 键 词：气相色谱-质谱联用 阿糖胞苷 氯甲烷 氯乙烷 2-氯丙烷 基因毒性杂质 

分 类 号：R917[医药卫生—药物分析学]