注射用头孢美唑钠高分子杂质鉴定方法研究  

Identification of Polymer Impurities in Cefmetazole Sodium for Injection

作　　者：韩彬 庞文哲 高燕霞 HAN Bin;PANG Wenzhe;GAO Yanxia(Hebei Institute for Drug Control,Shijiazhuang,Hebei,China 050011)

机构地区：[1]河北省药品检验研究院

出　　处：《中国药业》2019年第24期31-34,共4页China Pharmaceuticals

摘　　要：目的建立高效分子排阻色谱法检测头孢美唑钠中的聚合物的方法,并应用在线脱盐-高效液相色谱-离子阱-飞行时间质谱(2D-LC-IT-TOF/MS)法对其聚合物进行鉴定。方法色谱柱为WT-Cef-SEC柱(300 mm×7.8 cm,5μm),流动相为5 mmol/L乙酸铵-乙腈(95∶5,V/V),流速为0.6 m L/min,检测波长为254 nm,柱温为25℃,进样量为20μL,电喷雾离子源(ESI),正离子扫描模式;按不加校正因子的主成分自身对照法计算聚合物的含量。结果头孢美唑钠峰与聚合物峰分离良好。头孢美唑钠质量浓度线性范围为0.5~2.5μg/m L(r=0.9999,n=5),定量限为3 ng,检测限为1 ng。通过2D-LC-IT-TOF/MS推测出聚合物3为头孢美唑钠二聚体,聚合物2为头孢美唑钠三聚体。结论该方法适用于注射用头孢美唑钠高分子杂质的检测,为β-内酰胺类抗菌药物中聚合物的分离、分析及产品质量提高提供了依据。Objective To establish a high performance size exclusion chromatography(HPSEC)method for the content determination of the polymers in cefmetazole sodium,and to identify the polymers by on-line desalting-HPLC-ion trap time of flight-mass spectrometry(2D-LC-IT-TOF/MS).Methods The chromatographic column was WT-Cef-SEC column(300 mm×7.8 mm,5μm),the mobile phase was 5 mmol/L ammonium acetate-acetonitrile(95∶5,V/V),the flow rate was 0.6 m L/min,the detection wavelength was254 nm,the column temperature was 25℃,the sample size was 20μL.The ion source was ESI ionization source,the scan pattern was positive and the content of polymers was determined by main component selfcompare without calibration factor.Results The peak of cefmetazole sodium was well separated from the peak of polymers.The linear range of cefmetazole sodium concentration was 0.5-2.5μg/m L(r=0.9999,n=5).The LOQ of cefmetazole sodium was 3 ng,and the LOD of cefmetazole sodium was 1 ng.Polymer 3 was conjectured to be the dimer of cefmetazole sodium and Polymer 2 was conjectured to be the trimer of cefmetazole sodium by 2D-LC-IT-TOF/MS.Conclusion The method is suitable for the determination of polymer impurities in Cefmetazole Sodium for Injection,which provides a basis for the separation and analysis of polymers inβ-lactam antibiotics and the improvement of products’quality.

关 键 词：头孢美唑钠 高分子杂质 高效分子排阻色谱法 在线脱盐-高效液相色谱-离子阱-飞行时间质谱 

分 类 号：R917[医药卫生—药物分析学] R978.1[医药卫生—药学]