头孢克肟颗粒有关物质测定方法的改进

Improvement of determination method for cefixime granules related substances

目的:改进头孢克肟颗粒有关物质的液相色谱测定方法。方法:使用高效液相色谱仪,选择YMC-Triart C_(18)色谱柱(250 mm×4.6 mm,5μm),以0.05 mol·L^(-1)甲酸铵溶液(pH 4.7)-甲醇为流动相,流速1 mL·min^(-1),进行梯度洗脱,进样量为10μL,检测波长为254 nm。结果:将该色谱条件应用于头孢克肟颗粒有关物质的检测,对比了本文方法与药典方法(含USP PF 2018版)中有关物质测定方法之间的差异,并完成了专属性、线性、准确度、精密度和耐用性等系统的方法学验证。药典方法均无法同时使主要降解杂质A1~A4或杂质B1~B4基线分离,且无法用于测定聚合物杂质B及聚合物杂质D。本文方法头孢克肟、各特定杂质之间的分离度均符合要求(R≥1.5),可同时检测并定量聚合物B及聚合物D,分离度优于药典方法。结论:本方法改进了头孢克肟、各杂质间的分离度,杂质检出个数更多,能准确定量各特定杂质,灵敏度较高,重复性较好,适用于头孢克肟的质量控制。

Objective:To improve the liquid chromatographic determination method of cefixime granules related substance.Methods:High performance liquid chromatography was used,YMC-Triart C_(18) column(250 mm×4.6 mm,5μm)was selected,0.05 mol·L^(-1) ammonium formate solution(pH 4.7)-methanol was used as mobile phase,flow rate was 1 mL·min^(-1),and gradient washing was carried out.The injection volume was 10μL.The detection wavelength was 254 nm.Results:This chromatographic condition was applied to the detec⁃tion of cefixime granules.The differences between this method,the pharmacopeial method and the method of USP PF 2018 were compared,and the systematic methodological verification of specificity,linearity,accuracy,preci⁃sion and durability were completed.Using pharmacopeial methods,baseline separation of degradation impurities A1~A4 or impurities B1~B4 cannot be reached,and current methods cannot be used to determine polymer B and polymer D.The method proposed in this article can make the resolution between cefixime and each specific impurities meet the requirements(R≥1.5),and can detect and quantify polymer B and polymer D at the same time,and the resolution was better than the current method.Conclusion:This method improves the separation between cefixime and impurities,more impurities is detected and can accurate quantify specific impurities.This method has high sensitivity and good repeatability,and is suitable for the quality control of cefixime.