目的 研究注射用氯唑西林钠的杂质谱,鉴定主要杂质的结构、明确杂质来源及与生产工艺之间的关系。方法 分别采用优化后的反相HPLC和正相HPLC系统对国内7家企业样品进行杂质谱研究,采用半制备技术对主要杂质进行制备,综合应用LC-QTOF-MS、¹H-NMR和¹³C-NMR技术对杂质结构进行确认。结果 结合生产工艺分析,检测出1种与成盐工艺相关的杂质、1种与纯化工艺相关的杂质,同时首次检测出4种新杂质。结论 本实验的研究方法 可对国产注射用氯唑西林钠的杂质进行更全面的检测,对提高产品质量具有重要意义。

OBJECTIVE To investigate the impurity profile of cloxacillin sodium for injection and study the source of major impurities. METHODS The impurities in samples from seven manufacturers were profiled by an optimized reversed-phase HPLC method and a newly established normal-phase HPLC method. The major impurities were prepared by semi preparation technology and identified by LC-QTOF-MS,¹H-NMR and ¹³C-NMR.RESULTS Two new impurities relating with the salt-forming reaction and the purification process respectively,and four other new impurities were all successfully identified in this study.CONCLUSION The study is suitable for profiling the impurities in cloxacillin sodium for injection and is quite useful for enhancing the quality control.