UPLC-MS/MS法测定利奈唑胺原料和葡萄糖注射液中的叠氮类遗传毒性杂质  

Determination of azide genotoxic impurity in linezolid API and glucose injection by UPLC-MS/MS

作　　者：彭诗雁 陈华[2] 尹婕[2] PENG Shiyan;CHEN Hua;YIN Jie(School of Pharmacy,China Pharmaceutical University,Nanjing 211198;National Medical Products Administration Key Laboratory for Quality Research and Evaluation of Chemical Drugs,National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]中国药科大学药学院,南京211198 [2]中国食品药品检定研究院,国家药品监督管理局化学药品质量研究与评价重点实验室,北京102629

出　　处：《中国药科大学学报》2022年第6期705-709,共5页Journal of China Pharmaceutical University

基　　金：国家药品监督管理局化学药品质量研究与评价重点实验室学科建设资助项目(No.1030050090124)

摘　　要：建立了一种超高效液相色谱-串联质谱法(UPLC-MS/MS)测定利奈唑胺原料及其葡萄糖注射液中的遗传毒性杂质(R)-5-(叠氮甲基)-3-[3-氟-4-(4-吗啉基)苯基]-2-唑烷酮。采用Acquity UPLC HSS T3色谱柱(100 mm×2.1 mm,1.8μm)进行色谱分离,以0.1%甲酸水-0.1%甲酸乙腈(60∶40)为流动相,流速为0.3 mL/min进行等度洗脱;采用电喷雾离子化,在正离子模式下多反应监测模式进行监测。结果表明,该遗传毒性杂质在质量浓度4~12 ng/mL内线性关系良好,定量限为0.073 ng/mL,低、中、高浓度(80%、100%、120%限度浓度)加样溶液平均回收率分别为101.14%、100.59%和101.47%(RSD分别为0.73%、1.10%、0.91%)。同时,该遗传毒性杂质供试品溶液在6 d内稳定,3批制剂及2批原料中均未检出(R)-5-(叠氮甲基)-3-[3-氟-4-(4-吗啉基)苯基]-2-唑烷酮。A UPLC-MS/MS method was established for the determination of the genotoxic impurity(R)-5-(azidomethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinone in linezolid API and its glucose injection.Chromatographic separation was performed on a Waters Acquity UPLC HSS T3 column(100 mm×2.1 mm,1.8μm)with 0.1%formic acid water-0.1%formic acid acetonitrile(60∶40)at a flow rate of 0.3 mL/min.The UPLC-MS/MS was equipped with electrospray ionization in positive ionization mode and multiple reaction monitoring mode.The results showed that the calibration curve was linear in the range of 4-12 ng/mL and the limit of quantification was 0.073 ng/mL.The average recoveries of the low,medium and high concentration(80%,100%,120%limit concentration)loading solutions were 101.14%,100.59%and 101.47%,respectively(RSDs:0.73%,1.10%and 0.91%,respectively).The sample solution was stable for 6 d.No genotoxic impurity of(R)-5-(Azidomethyl)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxazolidinonewas not detected in the samples of linezolid API and its glucose injection.

关 键 词：超高效液相色谱-串联质谱法 利奈唑胺 遗传毒性杂质 (R)-5-(叠氮甲基)-3-[3-氟-4-(4-吗啉基)苯基]-2-唑烷酮 含量测定 

分 类 号：R917[医药卫生—药物分析学]