UHPLC-HRMS定量检测莫西沙星中5种亚硝胺类化合物  

Quantitative Determination of 5 Nitrosamines in Moxifloxacin by UHPLC-HRMS

作　　者：李霄[1] 王娜[1] 张娜 唐胜华 韩春乐 黄乾阳 张志英 张雅妮 李安平 李振[1,4] LI Xiao;WANG Na;ZHANG Na;TANG Shenghua;HAN Chunle;HUANG Qianyang;ZHANG Zhiying;ZHANG Yani;LI Anping;LI Zhen(Binhai Industrial Technology Research Institute,Zhejiang University,Tianjin 300451,China;Harmonia Testing(Tianjin)Co.,Ltd.,Tianjin 300457,China;Shanxi Nuocheng Pharmaceutical Co.,Ltd.,Huairen 038300,China;Shanghai Yunxiang Medical Technology Co.,Ltd.,Shanghai 201802,China)

机构地区：[1]浙江大学滨海产业研究院,天津300451 [2]瀚盟测试科技(天津)有限公司,天津300457 [3]山西诺成制药有限公司,山西怀仁038300 [4]上海韵祥医学科技有限公司,上海201802

出　　处：《中国现代应用药学》2022年第1期82-86,共5页Chinese Journal of Modern Applied Pharmacy

基　　金：上海市科学技术委员会科研计划项目(18401933401)。

摘　　要：目的基于超高效液相色谱和高分辨质谱建立同时检测莫西沙星中5种亚硝胺类基因毒性杂质的定量分析方法。方法采用ACE Excel 1.7 C_(18)-PFP(100 mm×2.1 mm,1.7μm)色谱柱,0.1%甲酸水-甲醇为流动相,0.3 mL·min^(-1)的流速进行梯度洗脱。采用四极杆高分辨静电场轨道阱质谱在电喷雾正离子条件下运用平行反应监测模式对5种亚硝胺类化合物进行定量检测。结果5种亚硝胺类基因毒性杂质的定量限均≤0.5 ng·mL^(-1)。NPYP、NEMA和NDEA的标准曲线在1.0~100 ng·mL^(-1)(NPIP和NDBA为0.1~100 ng·mL^(–1))呈良好线性关系(R^(2)≥0.998)。该方法在盐酸莫西沙星药物中的回收率为93.1%~114.1%,RSD为0.7%~4.6%。结论本方法结果准确、灵敏度高、重复性好,适用于盐酸莫西沙星中亚硝胺类基因毒性杂质的含量检测。OBJECTIVE To develop and validate a UHPLC/HRMS method for simultaneous quantitation of 5 genotoxic nitrosamines in moxifloxacin.METHODS ACE Excel 1.7 C_(18)-PFP(100 mm×2.1 mm,1.7μm)column was used,separated by gradient elusion using a mixture of water and methanol with 0.1%formic acid at 0.3 mL·min^(–1),and 5 nitrosamines were detected by parallel reaction monitoring using Q Exactive mass spectrometer in electrospray positive mode.RESULTS The lower limits of quantitation for 5 genotoxic nitrosamines≤0.5 ng·mL^(-1).Good linearity was established for NPYR,NEMA and NDEA over 1.0−100 ng·mL^(–1),and for NPIP and NDBA over 0.1−100 ng·mL^(-1)(R^(2)≥0.998),respectively.The intra-assay accuracy of 5 nitrosamines in moxifloxacin hydrochloride was determined to be from 93.1%to 114.1%,and the RSD was found to be from 0.7%to 4.6%.CONCLUSION The validated method provides satisfactory sensitivity and specificity for analysis of genotoxic nitrosamines as impurities in moxifloxacin hydrochloride.

关 键 词：盐酸莫西沙星 N-亚硝胺类 基因毒性杂质 超高效液相色谱-串联质谱法 平行反应监测 

分 类 号：R917.101[医药卫生—药物分析学]