HPLC-MS/MS分析盐酸头孢替安酯中未知杂质的结构  

Determination of Unknown Impurities in Cefotiam Hexetil by HPLC-MS/MS

作　　者：唐群星[1,2] 刘明东[1,2] 颜有仪[1] 叶懿[1] 王智慧[1,2] 詹兰芬[1] 廖林川[1] 

机构地区：[1]四川大学华西基础医学与法医学院毒物分析教研室,成都610041 [2]四川大学华西药学院,成都610041

出　　处：《四川大学学报（医学版）》2013年第3期481-484,493,共5页Journal of Sichuan University(Medical Sciences)

摘　　要：目的采用高效液相色谱-串联质谱联用(HPLC-MS/MS)对盐酸头孢替安酯原料药中的杂质进行结构解析。方法盐酸头孢替安酯原料药经去离子水溶解,采用HPLC-MS/MS技术进行分析。色谱柱为Agilent SB-C18柱(150mm×2.1mm,3.5μm),流动相为0.1%甲酸溶液(A)-乙腈(B)(97∶3),梯度洗脱,洗脱程序为〔t(min)/B(%)〕:0/3、5/3、15/20、20/40、30/60、40/80,流速0.3mL/min,检测波长254nm,柱温40℃;离子源为电喷雾离子源(ESI),正离子MRM模式扫描,电离电压4kV,锥孔电压100V,质量扫描范围(m/z)为50～1000,雾化气为氮气,雾化气压力40psi,干燥气温度350℃,干燥气流速10L/min。结果通过对盐酸头孢替安酯和有关物质的液相色谱图以及液相色谱峰对应的质谱图分析归纳,推测盐酸头孢替安酯样品中有关物质1为Δ3-异构体,并解析了有关物质2中的3个杂质的结构。结论本法可灵敏、快速、准确地分离鉴定盐酸头孢替安酯中的有关物质,对盐酸头孢替安酯的质量控制有指导意义。Objecitve To detect unknown impurities in raw drug material of cefotiam hexetil. Methods High performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） was employed for the determination of impurities in eefotiam hexetil. Agilent SB-C18 column （150 mm×2.1 mm i. d. , 3.5μm particles） was used for chromatographic separations of cofotiam hexetil dissolved in deionized water, with mobile phase consisting of （A） 0.1% formic acid and （B） acetonitrile and timed gradient program T （min）/B （%）： 0/3, 5/3, 15/20, 20/40, 30/60, 40/80. The flow rate was set at 0. 3 mL/min with DAD detector wavelength fixed at 254 nm. Electrospray ionization source was applied and operated in positive ion MRM mode. The source voltage was kept at 4 kV and cone voltage was 100 V with the mass range m/z 50-1000. Nitrogen was used as nebulizing gas and the nebulizer pressure was 40 psi. The drying gas temperature was 350 ℃ and the drying gas flow was 10 L/min. Results Unknown impurities of cefotiam hexetil were identified. Substance 1 was A3-isomer of cefotiam hexetil. The structures of 3 other substances were also determined. Conclusion The method is sensitive, rapid and credible for the analysis of cefotiam hexetil and its related impurities, which can be applied in quality control of cefotiam hexetil.

关 键 词：HPLC-MS MS盐酸头孢替安酯 杂质 

分 类 号：R927[医药卫生—药学]