HPLC-MS/MS法测定硝酸甘油注射液中的9种亚硝胺杂质
Determination of Nine Nitrosamine Impurities in Nitroglycerine Injection by HPLC-MS/MS
颜慷祺 1黄子健 1李同根 1李娜 1黎芷明 1王小婷 1朱翠娴 1周小琴1
作者信息
- 1. 广州白云山明兴制药有限公司,广东 广州 510250
- 折叠
摘要
目的:建立HPLC-MS/MS法测定硝酸甘油注射液中的亚硝胺杂质.方法:采用色谱柱ACE Excel 3 C18-PFP(3.0 mm×100 mm,3 μm);以0.1％甲酸水溶液为流动相A,甲醇为流动相B,梯度洗脱;流速为0.5 mL·min-1;柱温为40℃;样品盘温度5℃;进样体积为 5 μL.离子源为大气压化学离子源,检测方式为三重四极杆质谱-多反应监测模式;干燥气为氮气;干燥气温度为300℃;干燥气流速为4 L·min-1;雾化器压力为40 psi;毛细管电压为1500 V;蒸发室温度为350℃;电晕针电流为 6 μA.结果:建立的检测条件下,各亚硝胺杂质在 0.40 ng·mL-1～6.65 ng·mL-1之间线性关系良好,最小检测限为 0.12 ng·mL-1,最小定量限为0.40 ng·mL-1.平均回收率在89.7％～99.3％之间,平均RSD(n=9)在3.0％～5.5％之间.检测3 批样品,均未检出亚硝胺杂质.结论:本方法操作简便、灵敏度高、专属性强,可用于硝酸甘油注射液中9 种亚硝胺杂质的质量控制.
Abstract
Objective:To establish an HPLC-MS/MS method for the determination of Nitrosamine impurities in nitroglycerin injection.Method:The method were performed on ACE Excel 3 C18-PFP column(3.0 mm×100 mm,3 μm)with a gradient elution of 0.1％formic acid as the mobile phase A and methanol as the mobile phase B at a flow rate of 0.5 mL·min-1;the column temperature was set at 40℃;the sample plate temperature was 5℃;the injection volume was 5 μL.The ionisation mode was atmospheric pressure chemical ionization positive mode(APCI+)and the detection mode was triple quadrupole mass spectrometry-multiple reaction monitoring(QTOF-MRM);nitrogen was used as drying gas and temperature was 300℃with 4 L·min-1 flow rate;the nebuliser pressure was 40 psi;the capillary voltage was 1500 V;the heater temperature was 350℃and the corona current was 6 μA.Results:Under the detection parameters,each nitrosamine impurity had a good linearity which were between 0.40 ng·mL-1 and 6.65 ng·mL-1,the limits of detection(LOD)was 0.12 ng·mL-1,and the limits of quantification(LOQ)was 0.40 ng·mL-1.The average recovery ranges from 89.7％to 99.3％,and the average RSDs(n=9)were between 3.0％to 5.5％.Three batches of samples were tested and no nitrosamine impurities were detected.Conclusion:This method is simple to operate,highly sensitive and specific,and can be used for the quality control of nine nitrosamine impurities in nitroglycerin injection.
关键词
硝酸甘油注射液/亚硝胺杂质/HPLC-MS/MSKey words
nitroglycerin injection/nitrosamine impurities/HPLC-MS/MS引用本文复制引用
出版年
2024
NETL
NSTL
万方数据