依诺沙星制剂有关物质的研究

目的:采用高效液相色谱-三重串联四极杆质谱及超高分辨四极杆傅里叶变换离子回旋共振串联质谱仪对依诺沙星主要有关物质进行结构鉴定。方法:采用高效液相色谱法测定75批依诺沙星制剂中的有关物质,确定含量不低于0.1%的主要杂质。采用Thermo Accucore XL C₁₈色谱柱(4.6 mm×250 mm,4 μm)及高效液相色谱-三重串联四极杆质谱,以0.1%甲酸溶液(含5 mmol·L^-1醋酸铵)-甲醇-乙腈(86:5:9)为流动相A,以0.1%甲酸溶液(含5 mmol·L^-1醋酸铵)-甲醇-乙腈(350:325:325)为流动相B进行梯度洗脱,对依诺沙星有关物质进行分离,并初步测定主要有关物质准分子离子质荷比;采用傅里叶变换质谱法测定有关物质准确母离子及子离子,并结合对照品及裂解规律,对主要有关物质进行结构推定。结果:在所建立的高效液相色谱-三重串联四极杆质谱条件下,依诺沙星及其有关物质可达到良好分离。依诺沙星制剂中3个主要有关物质均具有依诺沙星的1,8-萘啶母核结构。结论:本研究对依诺沙星制剂中的主要有关物质进行了结构鉴定,为改进生产工艺和提高产品质量提供了参考依据。

Objective: To establish a liquid chromatography(LC-MS) and Fourier transform mass spectrometry (FT-MS) method to identify the structure of related substances in enoxacin preparation.Methods:The related substances in 75 batches of enoxacin preparation were determined by HPLC to confirm the main impurities that were not below 0.1%.The determinations were performed on a Thermo Accucore XL C₁₈ column(4.6 mm×250 mm,4 μm) and HPLC-Triple Quad MS;the mobile A was 0.1% formic acid solution(containing 5 mmol·L^-1 ammonium acetate)-methanol-acetonitrile(86:5:9)and the mobile B was 0.1% formic acid solution (containing 5 mmol·L^-1 ammonium acetate)-methanol-acetonitrile(350:325:325).The main related substances in enoxacin were separated by mobile phase and their quasi-molecular ion[M+H]+were roughly determined.FT-MS was used to determine the accurate parent ions and product ions.The structure identification of the main related substances were carried out by combining the reference substances and fragmentation regularities.Results: The peaks of enoxacin and the main related substances can be separated well in the established condition of HPLC-Triple Quad MS.The three main related substances all have the 1, 8-naphthyridine stem-nucleus of enoxacin.Their sources were related to the production process and crude drug.Conclusion: The structures of the main related substances in enoxacin preparation were ascertained through the study,which provides a reference for improving the production process and the quality of products.

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