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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

彭诗雁, 陈华, 尹婕. 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[J]. 中国药科大学学报, 2022, 53(6): 705-709. DOI: 10.11665/j.issn.1000-5048.20220609
引用本文: 彭诗雁, 陈华, 尹婕. 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[J]. 中国药科大学学报, 2022, 53(6): 705-709. DOI: 10.11665/j.issn.1000-5048.20220609
PENG Shiyan, CHEN Hua, YIN Jie. Determination of azide genotoxic impurity in linezolid API and glucose injection by UPLC-MS/MS[J]. Journal of China Pharmaceutical University, 2022, 53(6): 705-709. DOI: 10.11665/j.issn.1000-5048.20220609
Citation: PENG Shiyan, CHEN Hua, YIN Jie. Determination of azide genotoxic impurity in linezolid API and glucose injection by UPLC-MS/MS[J]. Journal of China Pharmaceutical University, 2022, 53(6): 705-709. 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

基金项目: 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)

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

Funds: This study was supported by the Discipline Construction Funding Project of National Medical Products Administration Key Laboratory for Quality Research and Evaluation of Chemical Drugs (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,1.8 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/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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    [2] Brickner SJ,Hutchinson DK,Barbachyn MR,et al. Synthesis and antibacterial activity of U-100592 and U-100766,two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant gram-positive bacterial infections[J]. J Med Chem,1996,39(3):673-679.
    [3] European Medicines Agency. ICH guideline M7(R1) on assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk-step 5[EB/OL].(2018-03-02)[2022-04-27]. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-m7r1-assessment-control-dna-reactive-mutagenic-impurities-pharmaceuticals-limit_en.pdf.
    [4] Tuberculosis branch of Chinese Medical Association,Expert consensus writing group on linezolid anti-tuberculosis treatment. Expert consensus on anti-tuberculosis treatment with linezolid[J]. Chin J Tuberc Respir Dis(中华结核和呼吸杂志),2018,41(1):14-19.
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出版历程
  • 收稿日期:  2022-07-03
  • 修回日期:  2022-11-24
  • 刊出日期:  2022-12-24

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