丙酸增强电喷雾离子化效率液质联用法推定硫酸依替米星检出有关物质的结构

袁耀佐,吴宇宁,赵卫,王昉,苏晓春,谭力,张玫,胡昌勤

中国药学杂志 ›› 2015, Vol. 50 ›› Issue (20) : 1790-1796.

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中国药学杂志 ›› 2015, Vol. 50 ›› Issue (20) : 1790-1796. DOI: 10.11669/cpj.2015.20.015
2015年版《中国药典》专栏

丙酸增强电喷雾离子化效率液质联用法推定硫酸依替米星检出有关物质的结构

  • 袁耀佐1,吴宇宁1,2,赵卫1,王昉2,苏晓春3,谭力1,张玫1*,胡昌勤4*
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Identification of the Related Substances in Etimicin Sulfate Detected Under the Condition of Chinese Pharmacopoeia 2010 by LC/MSn with Propionic Acid Enhanced Electrospray Ionization

  • YUAN Yao-zuo1, WU Yu-ning1,2, ZHAO Wei1, WANG Fang2, SU Xiao-chun3,TAN Li1, ZHANG Mei1* , HU Chang-qing4*
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摘要

目的 建立适用于硫酸依替米星在2015年版《中国药典》二部中第二法(2010年版条件下)检出有关物质并进行结构鉴定的LC/MSn法。方法 采用Welch Ultimate LP-C18(4.6 mm×300 mm,5 μm)色谱柱,以0.2 mol·L-1三氟乙酸(添加0.1%的丙酸)-甲醇(84∶16)为流动相;流速:1.0 mL·min-1;柱后分流,30%进入质谱检测,用有关物质色谱保留时间、一级、二级质谱信息推测结构。结果 在2010年版《中国药典》的流动相条件中添加0.1%的丙酸,显著提高质谱检出灵敏度,且依替米星及其有关物质的保留时间无明显改变,代表性样品中检测出了28个有关物质,利用杂质对照品鉴定了9个,利用质谱碎片信息推定了14个,其余5个因质谱信息有限未进行推定。结论 建立的方法可以用于2010年版《中国药典》条件下检出有关物质的结构推定,为硫酸依替米星质量提高和工艺优化提供了参考。

Abstract

OBJECTIVE To establish an LC/MSn method for identification of the related substances in etimicn sulfate detected under the chromatographic condition described in Chinese Pharmacopoeia 2010.METHODS The HPLC separation was carried out on a Welch Ultimate LP-C18 column(4.6 mm×300 mm,5 μm)with mobile phase consisting of 0.2 mol·L-1trifluoroacetic acid(containing 0.1% propionic acid )-methanol(84∶16) at a flow rate of 1.0 mL·min-1. Thirty percent of the eluent was detected by ion trap mass spectrometry, and the parent ions and the corresponding product spectra of all the related substances in etimicin sulfate were determined and elucidated.RESULTS Addition of 0.1% propionic acid into the mobile phase significantly enhanced the sensitivity of MS detector without altering the chromatographic behavior such as retention time and elution order of the related substances. Twenty-eight related substances were separated and detected by the LC/MSn method in a typical sample. Nine of them were identified with the help of corresponding impurity reference substances and 14 of them were elucidated by MS fragment information, while the other five were not identified due to limitated information. CONCLUSION The established method can be applied to the identification of the related substances in etimicn sulfate detected under the chromatographic condition described in Chinese Pharmacopoeia 2010, which is helpful to the quality improvement and process optimization of etmicin sulfate.

关键词

氨基糖苷类抗生素 / 硫酸依替米星 / 有关物质 / 液质联用 / 结构确证 / 丙酸

Key words

aminoglycoside antibiotics / etimicin sulfate / related substance / LC/MS / identification / propionic acid

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导出引用
袁耀佐,吴宇宁,赵卫,王昉,苏晓春,谭力,张玫,胡昌勤. 丙酸增强电喷雾离子化效率液质联用法推定硫酸依替米星检出有关物质的结构[J]. 中国药学杂志, 2015, 50(20): 1790-1796 https://doi.org/10.11669/cpj.2015.20.015
YUAN Yao-zuo, WU Yu-ning, ZHAO Wei, WANG Fang, SU Xiao-chun,TAN Li, ZHANG Mei , HU Chang-qing. Identification of the Related Substances in Etimicin Sulfate Detected Under the Condition of Chinese Pharmacopoeia 2010 by LC/MSn with Propionic Acid Enhanced Electrospray Ionization[J]. Chinese Pharmaceutical Journal, 2015, 50(20): 1790-1796 https://doi.org/10.11669/cpj.2015.20.015
中图分类号: R917   

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