气相色谱-串联质谱法测定芬地柞酸左旋氯哌斯汀中N-亚硝基二甲胺和N-亚硝基二乙胺含量  

Content Determination of N-Nitrosodimethylamine and N-Nitrosodiethylamine in Levocloperastine Fendizoate by GC-MS/MS

作　　者：王璐 刘峰 WANG Lu;LIU Feng(Sichuan Institute for Drug Control·Sichuan Testing Center of Medical Devices·NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation,Chengdu,Sichuan,China 611731)

机构地区：[1]四川省药品检验研究院·四川省医疗器械检测中心·药物制剂体内外相关性技术研究重点实验室,四川成都611731

出　　处：《中国药业》2021年第15期81-85,共5页China Pharmaceuticals

摘　　要：目的建立同时测定芬地柞酸左旋氯哌斯汀中的遗传毒性杂质N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)含量的气相色谱-串联质谱(GC-MS/MS)法。方法气相色谱条件中,色谱柱为安捷伦DB-WAX毛细管柱(30 m×0.25 mm,0.5μm);程序升温,恒流模式;流速为1.0 m L/min;载气为氦气;进样口温度为250℃,脉冲不分流进样,进样压力为15 psi,持续时间为1.5 min,进样量为2μL。质谱条件中,检测器为三重四极杆串联质谱检测器;离子源为电子轰击离子源;采集模式为多反应监测模式。结果 NDMA和NDEA质量浓度分别在0.922 2~46.109 3 ng/m L和0.235 6~11.781 0 ng/m L范围内与峰面积线性关系良好,r分别为0.998 3和0.999 8(n=6);NDMA的检测限为0.139 00 ng/m L,NDEA的检测限为0.045 83 ng/m L;NDMA的精密度、稳定性、重复性试验结果均符合要求(n=6);NDMA与NDEA的加样回收率分别为96.82%和95.93%,RSD分别为4.32%和6.58%(n=9)。结论所建立的方法结果准确灵敏,重复性好,可用于芬地柞酸左旋氯哌斯汀中NDMA和NDEA的含量测定。Objective To establish a gas-chromatography tandem mass spectrometry(GC-MS/MS)method for the simultaneous determination of genotoxic impurities of N-Nitrosodimethylamine(NDMA)and N-Nitrosodiethylamine(NDEA)in levocloperastine fendizoate.Methods In the conditions of GC,the chromatographic column was Agilent DB-WAX capillary column(30 m×0.25 mm,0.5μm),temperature-programmed and phe constant current mode was adopted,the flow rate was 1.0 mL/min,the carrier gas was helium,the injection port temperature was 250℃,injection with pulse splitless,the injection pressure was 15 psi,the injection time was 1.5 min,and the injection volume was 2μL.In the condition of MS,the detector was triple quadrupole tandem mass spectrometer,the ion source was electron bombardment ion source,and the acquisition mode was multiple reaction monitoring(MRM)mode.Results The linear ranges of NDMA and NDEA were 0.9222-46.1093 ng/mL(r=0.9983,n=6)and 0.2356-11.7810 ng/mL(r=0.9998,n=6),respectively.The limits of detection(LOD)of NDMA and NDEA were 0.13900 ng/mL and 0.04583 ng/mL,respectively.The results of precision,stability and repeatability tests of NDMA could meet the requirements(n=6).The recoveries of NDMA and NDEA were 96.82%,95.93%with RSDs of 4.32%and 6.58%(n=9),respectively.Conclusion The established method is accurate,sensi-tive and reproducible,which can be used for the content determination of NDMA and NDEA in levocloperastine fendizoate.

关 键 词：芬地柞酸左旋氯哌斯汀 气相色谱-串联质谱法 N-亚硝基二甲胺 N-亚硝基二乙胺 含量测定 

分 类 号：R927.1[医药卫生—药学] R974.2