阿司匹林有关物质的色谱-质谱结构鉴定  

Structure identification of the related substances of aspirin by LC-MS techniques

作　　者：程婷婷 陆宇婷 杭太俊[1] 宋敏[1] CHENG Ting-ting;LU Yu-ting;HANG Tai-jun;SONG Min(Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学药物分析系,南京210009

出　　处：《药物分析杂志》2020年第10期1837-1847,共11页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:采用色谱-质谱联用技术鉴定阿司匹林的有关物质。方法:采用Inertsil-C8色谱柱(250mm×4.6 mm,5μm),以乙腈-水-甲酸为流动相,梯度洗脱,对阿司匹林有关物质进行分离,采用电喷雾离子化-飞行时间质谱法(ESI-TOF/MS)测定各有关物质母离子的准确质量和元素组成,三重四极杆质谱测定子离子特征,结合对照品对照确证有关物质结构。结果:在所建立的条件下,阿司匹林及其有关物质分离良好,检测并鉴定出15个主要有关物质,其中6个为欧洲药典收载的有关物质,9个未知有关物质新鉴定为未有文献报道的多个阿司匹林分子间的酯交换或同时脱水成羧酸酐的产物。结论:色谱-质谱联用技术能有效地分离鉴定阿司匹林中的有关物质,为其质量控制和稳定性研究提供技术支持。Objective:To identify the related substances of aspirin by LC-MS techniques.Methods:The separation of aspirin and its related substances was performed using Inertsil-C8(250 mm×4.6 mm,5 μm) column containing a mixture of acetonitrile,water,and formic acid as the mobile phase eluted with gradient program.The high resolution TOF/MS operated in ESI mode was used for the determination of the accurate mass and elemental composition of the parent ions of the related substances,and triple quadrupole tandem mass was employed for the product mass spectra.The structures of the related substances were then figured out through the elucidation of the fragment ions and comparison with reference substances.Results:Aspirin and its related substances were adequately separated under the established HPLC conditions.A total of 15 major related substances of aspirin were detected and identified by the hyphenated techniques.Among them,6 were listed in EP and the rest 9 unknown products were identified as the ester substitution or concomitant carboxylic anhydrate products between more aspirin molecules having not been reported before.Conclusion:The established LCMS method is effective for separation and identification of the related substances of aspirin,and provide technical support for the quality control and stability study of aspirin.

关 键 词：阿司匹林 2-(乙酰氧基)苯甲酸 非甾体类镇痛药 有关物质 降解产物 结构鉴定 色谱-质谱联用 

分 类 号：R917[医药卫生—药物分析学]