LC-MS/MS法测定三甲基间苯三酚原料药中N-亚硝基二甲胺和N-亚硝基二乙胺的含量  

Determination of N-nitrosodimethylamine and N-nitrosodiethylamine in trimethyl phloroglucinol by LC-MS/MS method

作　　者：杨越莛 郑枫[1] 蔡浒 柳文媛[1,2] YANG Yue-ting;ZHENG Feng;CAI Xu;LIU Wen-yuan(Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 211198;Zhejiang Center for Safety Study of Drug Substances(Industrial Technology Innovation Platform),Hangzhou 310018)

机构地区：[1]中国药科大学药物分析系,南京211198 [2]浙江省原料药安全研究中心(工艺技术创新平台),杭州310018

出　　处：《中南药学》2022年第2期405-409,共5页Central South Pharmacy

摘　　要：目的建立高效液相色谱-串联质谱法检测三甲基间苯三酚原料药中的基因毒性杂质N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)的含量。方法色谱柱为Inertsil ODS-3(150 mm×4.6 mm,5μm),流动相为0.1%甲酸溶液(A)-甲醇(B),按程序进行梯度洗脱,在大气压化学电离源下以正离子、多重反应监测模式进行检测。结果NDMA和NDEA的检测限分别为0.8454 ng·mL^(-1)和0.2340 ng·mL^(-1),定量限分别为2.818 ng·mL^(-1)和0.7800 ng·mL^(-1),线性范围分别为2.818~18.79 ng·mL^(-1)和0.7800~5.200 ng·mL^(-1)。结论该方法专属性强,灵敏度高,适用于三甲基间苯三酚原料药中NDMA和NDEA的测定。Objective To determine the genotoxic impurities named N-nitrosodimethylamine(NDMA)and N-nitrosodiethylamine(NDEA)in trimethyl phloroglucinol(TMP)by LC-MS/MS.Methods Inertsil ODS-3 column(150 mm×4.6 mm,5μm)was used,with gradient elution of 0.1% formic acid solution and methanol as mobile phase.The analytes were detected in an atmosphere pressure chemical ionization under positive ion mode with multiple reaction monitoring.Results For NDMA and NDEA,the LOD was 0.8454 ng·mL^(-1) and 0.2340 ng·mL^(-1),the LOQ was 2.818 ng·mL^(-1) and 0.7800 ng·mL^(-1),and the linear range was 2.818~18.79 ng·mL^(-1) and 0.7800~5.200 ng·mL^(-1),respectively.Conclusion The method is specific and sensitive,and can be used to determine the content of NDMA and NDEA in TMP.

关 键 词：N-亚硝基二甲胺 N-亚硝基二乙胺 基因毒性杂质 三甲基间苯三酚 液相色谱-串联质谱 

分 类 号：R917.101[医药卫生—药物分析学]