高效液相色谱-质谱法同时测定药品中10种亚硝胺类基因毒性杂质  

Simultaneous determination of 10 nitrosamines genotoxic impurities in pharmaceuticals by high performance liquid chromatography-mass spectrometry

作　　者：徐艳梅 韩佳芮 郝丽娟 盖成 高燕霞 XU Yanmei;HAN Jiarui;HAO Lijuan;GE Cheng;GAO Yanxia(Hebei Institute for Drug and medical device inspection,NMPA Key Laboraory for Quality Control and Evaluation of Generic Drug,Shijiazhuang 050227;Hebei University of Science and Technology,Shijiazhuang 050091)

机构地区：[1]河北省药品医疗器械检验研究院,国家药品监督管理局仿制药质量控制与评价重点实验室,石家庄050227 [2]河北科技大学,石家庄050091

出　　处：《化学分析计量》2024年第7期55-62,共8页Chemical Analysis And Meterage

摘　　要：建立了超高效液相色谱-质谱联用法同时测定盐酸二甲双胍片、盐酸雷尼替丁胶囊、阿奇霉素原料药和氯沙坦钾原料药中10种N-亚硝胺类基因毒性杂质的含量。采用Kintex F5柱(100 mm×3 mm,2.7μm)为分离柱,以0.1%(体积分数)甲酸水-甲醇作为流动相,流量为0.6 mL/min,梯度洗脱,柱温为40℃,进样量为5μL。离子源为大气压化学电离源,采用多反应监测模式进行正离子扫描。10种N-亚硝胺类基因毒性杂质的质量浓度在1.0~104.2 ng/mL的线性范围内与色谱峰面积线性关系良好,相关系数均大于0.9995,检出限为0.1004~0.1042 ng/mL,定量限为0.0335~0.0347 ng/mL。样品平均加标回收率为91.73%~101.31%,测定结果的相对标准偏差为1.08%~3.67%(n=9)。该方法专属性强、灵敏度高,适用于同时测定盐酸二甲双胍、盐酸雷尼替丁、阿奇霉素和氯沙坦钾中的10种N-亚硝胺类基因毒性杂质。An ultra-high performance liquid chromatography-mass spectrometry method was established for the simultaneous determination of 10 N-nitrosamine genotoxic impurities in metformin hydrochloride tablets,ranitidine hydrochloride capsules,azithromycin raw materials and losartan potassium raw materials.Kintex F5 column(100 mm×3 mm,2.7μm)was used as the separation column,and 0.1%(volume fraction)formic acid water-methanol was used as the mobile phase.The flow rate was 0.6 mL/min,and the gradient elution was performed.The column temperature was 40℃,and the injection volume was 5μL.The ion source was an atmospheric pressure chemical ionization source,and the positive ion scanning was carried out in a multi-reaction monitoring mode.The mass concentration of 10 N-nitrosamine genotoxic impurities had a good linear relationship with the chromatographic peak area in the linear range of 1.0-104.2 ng/mL,and the correlation coefficients were all greater than 0.9995.The detection limits were 0.1004-0.1042 ng/mL,and the limits of quantitation were 0.0335-0.0347 ng/mL.The average recoveries of spiked samples were 91.73%-101.31%,and the relative standard deviations of determination results were 1.08%-3.67%(n=9).The method has strong specificity and high sensitivity,and is suitable for simultaneous determination of metformin hydrochloride and hydrochloric acid.

关 键 词：超高效液相色谱-质谱法 盐酸二甲双胍片 盐酸雷尼替丁胶囊 阿奇霉素 氯沙坦钾 基因毒性杂质 N-亚硝胺类杂质 

分 类 号：O657.7[理学—分析化学]