顶空气相色谱-质谱法测定交沙霉素及其制剂中N-亚硝基二甲胺  

Determination of N-nitrosodimethylamine in josamycin and its preparations by headspace gas chromatography-mass spectrometry

作　　者：邓鸣 曾庆花 梁秋霞 彭斌 卢日刚 朱健萍 DENG Ming;ZENG Qinghua;LIANG Qiuxia;PENG Bin;LU Rigang;ZHU Jianping(Guangxi Institute for Drug Control,Nanning 530021,China;Guilin Pharmaceutical Co.,Ltd.,Guilin 541004,China)

机构地区：[1]广西壮族自治区药品检验研究院,南宁530021 [2]桂林南药股份有限公司,广西桂林541004

出　　处：《化学分析计量》2025年第2期8-11,24,共5页Chemical Analysis And Meterage

基　　金：广西科技重大专项(桂科AA22096025);广西药品安全科研项目计划[桂药监科2022-08(直属)]。

摘　　要：建立顶空气相色谱-质谱法测定交沙霉素及其制剂中遗传毒性杂质N-亚硝基二甲胺(NDMA)的含量。样品采用二甲亚砜溶解,色谱柱为DB-WAX UI(30 m×0.25 mm,0.25μm),程序升温,进样口温度为220℃,载气为高纯氦气,恒流模式,流量为1.0 mL/min,顶空平衡温度为130℃,平衡时间为20 min。采用电子轰击源(EI),电离能量为70 eV,离子源温度为230℃,检测模式为多反应监测模式。NDMA在质量浓度为2.467~49.330 ng/mL时与色谱峰面积线性关系良好,相关系数为0.9998,检出限为4 ng/g。样品加标回收率为95.64%~117.50%,测定结果的相对标准偏差为8.3%(n=6)。初步分析NDMA来源于原料生产过程,提示原料生产企业关注物料的质量及工艺的优化。该方法准确灵敏、专属性强,可用于交沙霉素及制剂中遗传毒性杂质NDMA的质量控制。A headspace gas chromatography-mass spectrometry method was established for the determination of genotoxic impurity N-nitrosodimethylamine(NDMA)in josamycin and its preparations.The sample was dissolved in dimethylsulfoxide.The chromatographic column was DB-WAX UI(30 m×0.25 mm,0.25μm),and the column temperature was programmed.The temperature of the injection port was 220℃,the carrier gas was high purity helium,and the flow rate was 1.0 mL/min in constant current mode.The headspace equilibrium temperature was 130℃,the equilibrium time was 20 min.Electron bombardment source was used,the ionization energy was 70 eV,the ion source temperature was 230℃.The detection mode was multiple reaction monitoring.NDMA had a good linear relationship with the chromatographic peak area when the mass concentration was 2.467-49.330 ng/mL,the correlation coefficient was 0.9998,and the detection limit was 4 ng/g.The recoveries of sample spiked were 95.64%-117.50%,and the relative standard deviations of the determination results were 8.3%(n=6).Preliminary analysis showed that NDMA came from the production process of raw materials,prompting raw material manufacturers to pay attention to the quality of materials and the optimization of production technology.The method is accurate,sensitive and specific,which can be used for the quality control of josamycin and the genotoxic impurity NDMA in the preparation.

关 键 词：交沙霉素 N-亚硝基二甲胺 顶空气相色谱-质谱法 遗传毒性杂质 

分 类 号：O657.7[理学—分析化学]