LC-MS法鉴定头孢特仑新戊酯中的有关物质

Identification of the related substances in cefteram pivoxil by LC-MS

目的建立鉴定头孢特仑新戊酯中有关物质的液相色谱-质谱联用分析方法,测定头孢特仑新戊酯原料药和制剂产品中的有关物质。方法采用Syncronis C18(250 mm×4.6mm,5μm)色谱柱,10mmol·L-1乙酸铵-乙腈(体积比50∶50)作为流动相等度洗脱分离;采集各有关物质的UV谱、一级和二级质谱图,并根据所得信息对有关物质进行结构分析。结果头孢特仑新戊酯原料药中检测到8种有关物质,分别为6种合成副产物、1种水解产物和1种降解产物;制剂产品中除原料药中的8种有关物质外,还检测到4种新的有关物质,分别为2种氧化产物、1种水解产物和1种降解产物。结论该方法灵敏度高,全面系统的阐述了头孢特仑新戊酯中的有关物质,为其质量控制和工艺优化提供了参考依据。

Objective To develop the LC-MS method for the identification of the related substances of cefteram pivoxil in the API and the formulation product of cefteram pivoxil.Methods The chromatographic separation was achieved on a Syncronis C18 column with a mobile phase consisting of 10 mmol·L^-1 ammonium acetate solution and acetonitrile（V ∶ V=50 ∶ 50）.The results were obtained by ESI-MS and tandem mass spectrometry.The UV,parent ions and the corresponding product spectra of all the related substances in cefteram pivoxil were determined and elucidated.Results Eight related substances in cefteram pivoxil（bulk drug） were detected by the LC-MS / MS method and the structures were elucidated.Cefteram pivoxil（bulk drug） contains six by-products,one hydrolyzate and one degradation product; other than the eight related substances in the bulk drug,four new related substances were detected in the cefteram pivoxil tablets,including two oxidation products,one hydrolyzate and one degradation product.Conclusions The established method is effective for the identification of the related substances in cefteram pivoxil and the results are useful for its quality control and process optimization.