毛细管区带电泳检测磷霉素的杂质谱

Impurity profiling of fosfomycin by capillary zone electrophoresis

目的采用毛细管区带电泳(CZE)-间接紫外检测技术检测磷霉素的杂质谱。方法在CZE系统中采用同时含阳离子探针和阴离子探针的背景电解质,分别为无光吸收特征的阳离子组分和阴离子组分提供背景吸收并同时检测和筛查,以便得到磷霉素较为完整的杂质谱;为证实分离系统的专属性和有效性,分别采用杂质对照品、半制备HPLC和梯度洗脱HPLC-电喷雾离子阱质谱对杂质谱中的主要杂质进行了确认。结果采用该方法可将国外药典的HPLC系统难以分离的杂质与磷霉素分离,可从磷霉素的粗品中可分离出7个已知杂质和至少19个未知杂质,可检测在HPLC系统中难以检测的磷霉素的强保留杂质。结论该方法可应用于磷霉素的杂质谱检测。

Objective A capillary zone electrophoresis （CZE） method was established to detect the impurity profile of fosfomycin. Methods In order to obtain full impurity profile, a background electrolyte containing both an anionic probe and a cationic probe in a CZE system was used to simultaneously detect anionic ions and cationic ions possessing no chromophore in fosfomycin. Impurity reference standards, semi-preparative HPLC, and gradient HPLC electrospray ion trap mass spectrometry were used to confirm the selectivity and validity of the separation system. Results Using the novel method, 7 known impurities and at least 19 unknown impurities could be separated from a raw sample, while the pharmacopeia HPLC method might be difficult to separate most of these impurities, especially for the strong retained impurities. Conclusion This method can be used for the impurity profiling of fosfomycin.