西洛他唑有关物质的色谱-质谱结构鉴定  

Structure identification of related substances in cilostazol with hyphenated techniques

作　　者：顾霄 康铁纯 郑金琪 

机构地区：[1]浙江省食品药品检验研究院,杭州310000 [2]浙江工业大学,杭州310000

出　　处：《药物分析杂志》2015年第11期1971-1981,共11页Chinese Journal of Pharmaceutical Analysis

基　　金：浙江省科技厅分析测试科技计划项目(2014C37059)

摘　　要：目的:采用色谱-质谱联用技术对西洛他唑有关物质进行结构鉴定。方法:采用Waters XTerra RP-8(100 mm×4.6mm,3.5μm)色谱柱串联Agilent Eclipse XDB-C8(12.5 mm×4.6 mm,5μm)保护柱,以水-乙腈为流动相梯度洗脱,流速为1.0 m L·min-1,检测波长为254 nm,对西洛他唑有关物质进行分离;采用电喷雾正离子化的方法,通过飞行时间质谱(TOF)测定一级质谱精确质量,三重四极杆/线性离子阱质谱(Q-TRAP)扫描二级与三级质谱,并进行结构解析。飞行时间质谱(TOF)和三重四极杆/线性离子阱质谱(Q-TRAP)的喷雾电压、雾化气压力、去溶剂温度依次分别为4 k V和5.5 k V、240 k Pa和275 k Pa、350℃和480℃。结果:西洛他唑与其有关物质分离良好,检测出8个有关物质,其中4个尚未见文献报道,并综合分析鉴定了有关物质结构。它们大部分具有6-[4-(1-环己基-1H-戊四唑-5-基)丁氧基-2(1H)-喹诺酮结构,制剂中有关物质状态与原料药中的相似。结论:色谱-质谱联用技术能有效地鉴定西洛他唑中有关物质,为其工艺和质量控制提供参考依据。Objective：To identify the related substances in cilostazol coupled to time-of-flight mass spectrometry（TOF） and triple quadru by high performance liquid chromatography pole-linear ion trap mass spectrometry （QTRAP） hyphenated techniques. Methods： A Waters XTerra RP-8 （ 100 mm × 4.6 mm, 3.5μm） column and a Agilent Eclipse XDB-Cs （12.5 mm× 4.6 mm,5 μm） guard column were used for the separation of the related substances. The mobile phase consisted of acetonitrile and water using a gradient program at a flow rate of 1.0 mL · min^-1 with 254 nm detection. Electrospray ionization source was operated in positive ion mode. The structures of the related substances were speculated by TOF for accurate ion mass determination and by Q-TRAP for product ion scanning. The conditions of TOF and Q- TRAP were as follows ： the spray voltage 4 kV and 5.5 kV, the nitrogen draying gas nebulizer pressure 240 kPa and 275 kPa, the Cilostazol and the related substances were well separated gas temperature 350 ℃ and 480 ℃, respectively. Results： Eight related substances in cilostazol,4 in which had not been reported previously,were characterized mostly as the same frame structure of 6-[ 4-（ 1- cyclohexyl-1 H-tet- razol-5-yl） butoxy]-2 （1H）-Quinolinone by hyphenated techniques. The impurity profiles for the preparations were similar with the API. Conclusion：The hyphenated LC-MS method is useful for the identification of related substances in cilostazol. The results obtained are valuable for its manufacturing process and quality control.

关 键 词：西洛他唑 有关物质 杂质质谱裂解途径 色谱柱串联 飞行时间质谱 三重四极杆/线性离子阱质谱 

分 类 号：R917[医药卫生—药物分析学]