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
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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。
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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
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/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. -
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