Abstract：Objective To choose the best quantitative method and improve the assay of related substances by the determination of the relative correction factors of impurities A~F in cefixime granules for injection with the established method. Methods The chromatographic column using the 18-alkyl silane bond silica gel as a filler uses a 0.1% tetrabutylammonium hydroxide solution (pH to 6.0 with phosphoric acid) as the mobile phase A, acetonitrile as the mobile phase B, and equal degree elution. The column temperature was 40℃, and the detection wavelength was 254nm. The correction factors of each impurity were measured separately, and the results were compared with the principal component’s own comparison method and the external standard method. Results The separation of cefixime from adjacent impurity and known impurity was good. The linear relationship between cefixime, impurity A~E and impurity F was good in the concentration range of 0.5μg/mL (r＞0.996). The correction factors of impurity A~F were 2.7, 1.1, 1.1, 1.0, 1.0, and 1.1, respectively. Calculated by the self-control method of the correction factors, the results of 3 batches of samples were as follows. Impurity A were 0.46%, 0.51% and 0.50%. Impurity B were 0.07%, 0.06% and 0.07%. Impurity E were 0.09%, 0.10% and 0.09%, and impurity C, D and F were not detected. Other single largest impurities were all less than 0.1%, and the corrected total impurities were 0.81%, 0.67% and 0.65%, respectively. Calculated by external bid method, the results of 3 batches samples were as follows. Impurity A were 0.48%, 0.54% and 0.52%. Impurity B were 0.07%, 0.06% and 0.07%. Impurity E were 0.09%, 0.10%, 0.09%, and impurity C, impurity D, and impurity F were not detected. Other single largest impurities were all less than 0.1%, and the corrected total impurities were 0.83%, 0.70%, and 0.67%, respectively. There was no obvious difference between the two methods of calculation. The quantitative method of impurity was appropriate for the main component control method of the added correction factor. Conclusion Through the determination of each known impurity correction factor, the relevant substances of cefixime particles can be accurately determined without continuous supply of impurity reference materials. The operation of this method is simple and the results are accurate and reliable. It can provide a reference for improving the quantitative method of other dosage forms of the antibiotic.
苏燕琼 蔡国伟 高琳. 加校正因子的主成分自身对照测定头孢克肟颗粒的有关物质#br#[J]. 中国抗生素杂志, 2020, 45(08): 775-780.
Su Yan-qiong, Cai Guo-wei and Gao lin. Determination of the related substances in cefixime granules for injection with correction factors#br#. CJA, 2020, 45(08): 775-780.