注射用头孢西丁钠杂质谱分析方法影响因素探讨

Study on the influence factors of impurity profiles of cefoxitin sodium for injection

目的采用计算机辅助设计试验,考察影响注射用头孢西丁钠有关物质色谱分析方法的主要因素并使目标因子达到最优,对注射用头孢西丁钠杂质谱分析方法进行优化。方法制备系统适用性混合溶液,确定目标因子。通过Plackett-Burman(PB)设计筛选显著因素;通过中心组合设计(CCD)设计进行优化并确定最佳色谱条件;采用质谱法分析有关物质结构。结果色谱柱参数、流动相参数和梯度程序等因素均对杂质分离分析有较大影响;在建立的最优色谱条件下,11个潜在杂质均能得到有效分离并被检测。杂质谱分析显示,不同企业产品杂质谱存在差异。结论使用计算机辅助设计优化色谱分析方法,可实现对潜在杂质的有效分析,为完善注射用头孢西丁钠质量标准和质量控制提供了指导。

Objective The computer-aided design experiment was used to investigate the main factors affecting the chromatographic analysis of related substances in cefoxitin sodium for injection and to optimize the objective attributes,and the impurity profile analysis method was optimized.Methods The system suitability solution was prepared,and the objective attributes was determined.The Plackett-Burman(PB)design was used to screen for significant factors,and the Central Composite Design(CCD)design was adopted to determine optimal chromatographic conditions.Mass spectrometry was used to identify the structure of the related substances.Results The column parameters,mobile phases,and the gradient program had great influences on the separation and analysis of impurities.With the optimal chromatographic conditions established,11 potential impurities were effectively separated and detected.Impurity profiles analysis showed that there were differences in the impurity profiles of samples produced by different enterprises.Conclusion The use of computer-aided design in optimizing chromatographic method can facilitate the effective analysis of potential impurities.The article provided the guidance for cefoxitin sodium for injection standard improvement and quality control of the preparation.