高效液相色谱-高分辨质谱联用法测定硫酸依替米星中有关物质

侯金凤,李珉,李文东,刘照振,车宝泉,王俊秋

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (10) : 817-825.

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中国药学杂志 ›› 2018, Vol. 53 ›› Issue (10) : 817-825. DOI: 10.11669/cpj.2018.10.013
论著

高效液相色谱-高分辨质谱联用法测定硫酸依替米星中有关物质

  • 侯金凤,李珉,李文东,刘照振,车宝泉,王俊秋*
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Identification of Related Substances in Etimicin Sulfate by HPLC-HRMS/MS

  • HOU Jin-feng, LI Min, LI Wen-dong, LIU Zhao-zhen, CHE Bao-quan, WANG Jun-qiu*
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摘要

目的 采用高效液相色谱-高分辨质谱联用法,分析硫酸依替米星的有关物质结构及来源。方法 采用宽范围的Gemini NX C18(4.6 mm×250 mm,5 μm)色谱柱,以[水-氨水-冰乙酸(96∶3.6∶0.4)]-甲醇(70∶30)为流动相,采用柱后分流模式,Q-Exactive 高分辨质谱检测。分析依替米星及有关物质的一级和二级质谱数据,归纳同类化合物的质谱裂解规律,根据该规律及未知化合物的一级、二级高分辨质谱数据推测各有关物质的结构并分析其来源。结果 采用该方法,两家企业生产的硫酸依替米星中共检出有关物质65个,其中A企业含有38个,B企业含有59个,32个为共有杂质。对54个有关物质进行了结构推测,另11个有关物质目前未推测出结构。两企业之间有关物质存在显著差异,分析了可能的合成工艺关键参数。结论 采用HPLC-HRMS/MS对硫酸依替米星有关物质进行分析,准确性更好,通过对有关物质溯源及结构分析,为该品种的工艺优化研究提供了理论依据。

Abstract

OBJECTIVE To establish an HPLC-HRMS/MS method for analyzing the structures and sources of the related substances in etimicin sulfate. METHODS The chromatographic separation was achieved on a broad pH range column with a basic elution system composed of[H2O-ammonia-glacial acid(96∶3.6∶0.4)]-methanol(70∶30). Twenty percent of the eluent was detected under positive electrospray ionization(ESI) by Q-Exactive mass spectrometry. The fragmentation pathways were elucidated according to the HRMS and HRMS/MS fragmentation of etimicin and some known compounds. Then the unknown related substances were identified by analyzing their HRMS and HRMS/MS fragmentation with the help of the rule. RESULTS Sixty-five related substances were detected by the HPLC-HRMS/MS method in the two samples from different companies,among which 38 were detected in the product of company A, 59 in that of company B, and 32 were detected for both companies. Fifty-four related substances were identified or deduced, and the other 11 were not able to be identified due to limited information. Based on the significant difference of impurity spectra between the two enterprises, the key parameters of the synthesis process were analyzed. CONCLUSION An HPLC-HRMS/MS method, which showes excellent accuracy, is developed to identify the related substances in etimicin sulfate. The resources and structures of the related substances are analyzed, which will be helpful to the process optimization.

关键词

硫酸依替米星 / 有关物质 / 结构鉴定 / 高效液相色谱-高分辨质谱联用

Key words

etimicin sulfate / related substances / identification / HPLC-HRMS/MS

引用本文

导出引用
侯金凤,李珉,李文东,刘照振,车宝泉,王俊秋. 高效液相色谱-高分辨质谱联用法测定硫酸依替米星中有关物质[J]. 中国药学杂志, 2018, 53(10): 817-825 https://doi.org/10.11669/cpj.2018.10.013
HOU Jin-feng, LI Min, LI Wen-dong, LIU Zhao-zhen, CHE Bao-quan, WANG Jun-qiu. Identification of Related Substances in Etimicin Sulfate by HPLC-HRMS/MS[J]. Chinese Pharmaceutical Journal, 2018, 53(10): 817-825 https://doi.org/10.11669/cpj.2018.10.013
中图分类号: R917   

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