阿替洛尔片有关物质的色谱-二级质谱结构鉴定  

Seperation and identification of related substances in atenolol tablets by LC-MS/MS

作　　者：闫研 殷果 秦斌 王思明 王铁杰 

机构地区：[1]深圳市药品检验研究院,深圳药品质量标准研究重点实验室,深圳518057

出　　处：《药物分析杂志》2017年第8期1441-1446,共6页Chinese Journal of Pharmaceutical Analysis

基　　金：2015年国家药品抽验项目

摘　　要：目的:建立液相色谱-二级质谱联用(LC-MS/MS)法对阿替洛尔片中的有关物质进行结构鉴定。方法:采用X-Bridge C18色谱柱(4.6 mm×250 mm,5μm),以0.1%三氟乙酸溶液-甲醇(90∶10)为流动相进行洗脱,LC-MS/MS法测定各有关物质的二级质谱,采用电喷雾离子源(ESI),正离子扫描模式,并对准分子离子的各个产物离子进行归属,对各杂质的可能结构进行推测。结果:阿替洛尔及其有关物质分离良好,共检测出4个有关物质,并进行定量和结构鉴定,其中2-(4-羟苯基)乙酰胺和2-4-[(2RS)-2,3-二羟丙氧基]苯基]乙酰胺2个有关物质为英国药典2015年版收载,2-4-[(RS)-2-羟丙氧基-3-氨基]苯基]乙酰胺和2-4-[(RS)-2-羟丙氧基,3-[N异丙基-N-乙酸)氨基)]苯基]乙酰胺2个有关物质未见报道。结论:本文所建立的LC-MS/MS法可以有效地分离分析阿替洛尔及其有关物质,对完善质量标准,加强药品质量控制具有重要意义。Objective： To establish an LC-MS/MS method for identification of the related substances in atenolol tablets. Methods： HPLC separation was carried out on an X-bridge C18 column （4.6 mm ×250 mm, 5 μm ）with a mobile phase consisting of 0.1% trifluoroacetic acid aqueous solutions and pure methanol （90：10 ）. Related substances were characterized by LC-MS/MS method. The MS was operated by an ESI source and positive ion scanning mode. According to the mass spectra of the related substances, the fragment profiles were explained, and the chemical structures were elucidated. Results： Atenolol and its main related substances were well separated. Four related substances in atenolol tablets were detected by LC-MS/MS. Their content and chemical structures were proposed. 2- （ 4-hydroxyphenyl ） acetamide and 2- [ 4- [ （ 2RS ） -2, 3-dihydroxypropoxy ] phenyl ]acetamide were identified to be the same as those recorded in British pharmacopoeia （ 2015 ）. 2- L 4- / （ RS ） - 2-hydroxypropoxy, 3-amino ] phenyl ] acetamide and 2- [ 4- [ （ RS ） -2-hydroxypropoxy, 3- （ N-isopropyl-N- acetic acid ） amino phenyl ] acetamide were not reported previously. Conclusion： The established LC-MS/MS method is effective in separation and identification of the related substances in atenolol tablets, which is useful for the drug quality control.

关 键 词：阿替洛尔 肾上腺素受体阻滞剂 羟基-氨基苯乙酰胺 羟基-苯乙酰胺 二羟丙氧基苯乙酰胺 羟基-异丙乙酸氨苯乙酰胺 结构鉴定 液相色谱-二级质谱联用法 

分 类 号：R917[医药卫生—药物分析学]