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

彭诗雁; 陈华; 尹婕

doi:10.11665/j.issn.1000-5048.20220609

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

摘要

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，1.8 μm）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。

Abstract: 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, 1.8 μm) 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/mLand 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.

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