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GC-MS法测定甲磺酸中3种甲磺酸烷基酯类遗传毒性杂质

陈忆铃, 冯江江, 杨海雪, 时雅萍, 李龙囡, 冯芳

陈忆铃, 冯江江, 杨海雪, 时雅萍, 李龙囡, 冯芳. GC-MS法测定甲磺酸中3种甲磺酸烷基酯类遗传毒性杂质[J]. 中国药科大学学报, 2020, 51(4): 472-478. DOI: 10.11665/j.issn.1000-5048.20200413
引用本文: 陈忆铃, 冯江江, 杨海雪, 时雅萍, 李龙囡, 冯芳. GC-MS法测定甲磺酸中3种甲磺酸烷基酯类遗传毒性杂质[J]. 中国药科大学学报, 2020, 51(4): 472-478. DOI: 10.11665/j.issn.1000-5048.20200413
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CHEN Yiling, FENG Jiangjiang, YANG Haixue, SHI Yaping, LI Longnan, FENG Fang. Determination of genotoxic impurities of alkyl methanesulfonates in methanesulfonic acid by gas chromatography–mass spectrometry[J]. Journal of China Pharmaceutical University, 2020, 51(4): 472-478. DOI: 10.11665/j.issn.1000-5048.20200413
Citation: CHEN Yiling, FENG Jiangjiang, YANG Haixue, SHI Yaping, LI Longnan, FENG Fang. Determination of genotoxic impurities of alkyl methanesulfonates in methanesulfonic acid by gas chromatography–mass spectrometry[J]. Journal of China Pharmaceutical University, 2020, 51(4): 472-478. DOI: 10.11665/j.issn.1000-5048.20200413
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GC-MS法测定甲磺酸中3种甲磺酸烷基酯类遗传毒性杂质

  • 1.

    中国药科大学药物分析系，南京 211198

  • 2.

    无锡市药品检验所，无锡 214028

  • 3.

    扬子江药业集团南京海陵药业有限公司，南京 210049

基金项目: 国家药典委员会药品标准制修订研究课题资助(No.ZG2018-4-03)

Determination of genotoxic impurities of alkyl methanesulfonates in methanesulfonic acid by gas chromatography–mass spectrometry

  • 1.

    Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 211198

  • 2.

    Wuxi Center for Drug Safety Control, Wuxi 214028

  • 3.

    Yangtze River Pharmaceutical Group Nanjing Hailing Pharmaceutical Co., Ltd.,Nanjing 210049,China

Funds: This study was supported by Chinese Pharmacopoeia Commission on the Research and Revision of Drug Standards (No. ZG2018-4-03)

摘要

    摘要
  • 摘要: 建立一种液液萃取GC-MS分析方法，用于测定甲磺酸中遗传毒性杂质甲磺酸甲酯、甲磺酸乙酯、甲磺酸异丙酯。采用甲基聚硅氧烷毛细管色谱柱，程序升温，进样口温度220 ℃，不分流高压进样；质谱正离子模式，选择性监测m/z 56、m/z 79、m/z 80及m/z 123离子。实验结果显示，甲磺酸甲酯、甲磺酸乙酯、甲磺酸异丙酯对应色谱峰之间实现了基线分离，空白提取溶液无干扰；3种遗传毒性杂质在37~1 480 ng/mL范围内线性关系良好，且不同浓度水平平均回收率分别为104.99%、107.26%及108.85%，RSD均不超过4.54%。该方法具有专属、灵敏、准确、稳定、通用性好的特点，已用于多种不同来源市售甲磺酸中甲磺酸烷基酯类杂质的检测和控制。
    Abstract: An analytical liquid-liquid extraction-gas chromatography–mass spectrometry (LLE-GC-MS) method was established for the determination of genotoxic impurities including methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS) and isopropyl methanesulfonate (IMS) in methanesulfonic acid. An Agilent HP-1MS capillary column (30 m × 0.32 m, 1 μm) was used for separating the analytes by programmed heating with the inlet temperature of 220 °C. Mass spectrometry was operated in positive ion mode, and selective ion monitors were set at m/z 80 for MMS, m/z 79 for EMS, m/z 123 for IMS and m/z 56 for internal standard butyl methanesulfonate (BMS). Results showed that the baseline separation of MMS, EMS and IMS was achieved, and the blank extraction solution had no interference; good linearity was achieved in the range of 37-1 480 ng/mL for three alkyl methanesulfonates; The mean recoveries of MMS, EMS, IMS were 104.99%, 107.26%,108.85%, respectively, with RSD ≤ 4.54%. The established method has the characteristics of good specific, sensitive, accurate, stable and versatility, and has been used for the detection and control of alkyl methanesulfonate impurities in methanesulfonic acid from a variety of manufacturers.
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    • 参考文献(18)
  • [1] Glowienke S, Frieauff W, Allmendinger T, et al. Structure-activity considerations and in vitro approaches to assess the genotoxicity of 19 methane-, benzene- and toluenesulfonic acid esters[J]. Mutat Res-Gen Tox En, 2005,581(1/2): 23-34.
    [2] Clapp NK, Craig AW, Toya Sr RE. Oncogenicity by methyl methanesulfonate in male RF mice[J]. Science, 1968, 3844(161): 913-914.
    [3] Pfister T, Chapelon AE. General 4-week toxicity study with EMS in the rat[J]. Toxicol Lett, 2009,190(3):271-285.
    [4] Coffing SL, Kenyon MO, Ackerman JI, et al. Evaluation of the in vivo mutagenicity of isopropyl methanesulfonate in acute and 28‐day studies[J]. Environ Mol Mutagen, 2015, 56(3):322-332.
    [5] European Medicines Agency. The following letter is intended for all marketing authorization holders for medicinal products containing active substances in the form of mesilates, (di) isetionates, tosilates or besilates (EMEA/44714/2008) [S]. London: European Medicines Agency, 2008.
    [6] Center for Drug Evaluation and Research. Guidance for industry: genotoxic and carcinogenic impurities in drug substances and products: recommended approaches (draft) [S]. Rockvill: U.S. Food and Drug Administration, 2008.
    [7] National Medical Products Administration. Technical guidance on genotoxicity testing (药物遗传毒性研究技术指导原则) [EB/OL]. (2018-03-12) [2020-05-07]. http://www.nmpa.gov.cn/WS04/CL2138/300523.html.
    [8] Chinese Pharmacopoeia Commision. Chinese Pharmacopoeia: Part 4 (中华人民共和国药典:四部)[S]. Beijing: China Medical Science Press, 2020: 527-530.
    [9] Teasdale A, Eyley SC, Delaney ED, et al. Mechanism and processing parameters affecting the formation of methyl methanesulfonate from methanol and methanesulfonic acid: an illustrative example for sulfonate ester impurity formation[J]. Org Process Res Dev, 2009,13(3):429-433.
    [10] Teasdale A, Delaney EJ, Eyley SC, et al. A detailed study of sulfonate ester formation and solvolysis reaction rates and application toward establishing sulfonate ester control in pharmaceutical manufacturing processes[J]. Org Process Res Dev, 2010, 14(4):999-1007.
    [11] Shen DD, Zhu JL, Wu GF, et al. Development of synthesis of phosphatidylinositol 3-kinases inhibitor puquitinib mesylate [J]. Chin J Org Chem（有机化学）, 2019, 39(9):2676-2680.
    [12] Elder D, Facchine KL, Levy JN, et al. An approach to control strategies for sulfonate ester formation in pharmaceutical manufacturing based on recent scientific understanding[J]. Org Process Res Dev, 2012, 16(11):1707-1710.
    [13] Ramjitt HG, Singh MM, Coddington AB, et al. Gas chromatographic/mass spectrometric analysis of methyl methanesulphonate and ethyl methanesulphonate in the bismesylate salt of DPI 201-106, a positive inotropic agent for the treatment of heart failure[J]. J Mass Spectrom, 1996, 31(8): 867-872.
    [14] Zhou J, Xu J, Zheng XY, et al. Determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid by derivatization followed by high-performance liquid chromatography with ultraviolet detection[J]. J Sep Sci ,2017,40(17):3414-3421.
    [15] European Directorate for Quality and Medicines＆HealthCare (EDQM). European Pharmacopoeia Supplement 7.1 [S]. Strasbourg: Council of Europe, 2011:3321.
    [16] Zhang CZ, Huang L, Wu ZG, et al. Determination of sulfonate ester genotoxic impurities in imatinib mesylate by gas chromatography with mass spectrometry [J]. J Sep Sci, 2016, 39(18):3558-3563.
    [17] Wollein U, Schramek N. Simultaneous determination of alkyl mesilates and alkyl besilates in finished drug products by direct injection GC/MS[J]. Eur J Pharm Sci, 2012, 45(1/2):201-204.
    [18] Qian C, Gou XL, Hu GH, et al. Determination of residual mesylate esters in lurasidone hydrochloride tablets by GC-MS/SIM[J]. Anal Instru（分析仪器）,2018(01):199-203.
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  • 收稿日期:  2020-05-07
  • 刊出日期:  2020-08-24

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