GC-MS/MS法测定阿莫西林原料药中12种N-亚硝胺类基因毒性杂质

Determination of N-nitrosamines 12 kinds of genotoxic impurities in amoxicillin API by GC-MS/MS

目的采用GC-MS/MS法,建立阿莫西林原料药中12种N-亚硝胺类化合物含量测定的方法。方法样品经二氯甲烷提取后,涡旋、离心、取上清液过滤,采用VF-WAXms(30m×0.25mm×0.25μm)毛细管气相色谱柱分离,选择性反应监测(SRM)进行定性定量检测。结果12种N-亚硝胺在0.5~200ng/mL浓度范围内线性关系良好,相关系数均在0.998以上;检测限为0.033~0.481ng/mL,定量限为0.110~1.604ng/mL;回收率在78.5%~106.6%之间。结论所建立的GC-MS/MS测定法专属性好、灵敏度高,可同时测定12种N-亚硝胺杂质,为阿莫西林原料药中基因毒性杂质的质量控制提供参考。

Objective A GC-MS/MS method was developed for the determination of 12 kinds of N-nitrosamines in amoxicillin API.Methods The sample was extracted by dichloromethane,and the supernatant was filtered.The sample was separated by a VF WAXms(30m×0.25mm×0.25μm)capillary gas chromatography column,and the selection reaction monitoring(SRM)was selected for the qualitative and quantitative detection.Results The linear range of N-nitrosamines was 0.5~200ng/mL,and the correlation coeffi cients were all above 0.998;the detection limits were 0.033~0.481ng/mL;the limits of quantification were 0.110~1.604ng/mL;the recoveries were between 78.5%and 106.6%.Conclusion The established GC-MS/MS method has good specificity and high sensitivity.The method can simultaneously determine 12 kinds of N-nitrosamine impurities,which provides a reference for the quality control of genotoxic impurities in amoxicillin API.