加校正因子的主成分自身对照法测定复方片剂中瑞格列奈有关物质

目的: 建立加校正因子的主成分自身对照法测定瑞格列奈盐酸二甲双胍片中瑞格列奈有关物质的含量。方法: 采用J&K WpH C₁₈色谱柱(4.6 mm×250 mm,5 μm),以30 mmol·L^-1磷酸二氢钾溶液(用磷酸调节pH至3.2)-乙腈为流动相,梯度洗脱,流速1.5 mL·min^-1,检测波长240 nm,柱温40℃,进样量20 μL。测定瑞格列奈和杂质A、B、C的线性方程,以斜率计算杂质相对于瑞格列奈的校正因子,用相对保留时间确定各杂质位置。并进行了方法学验证。用相对校正因子计算复方片剂中瑞格列奈杂质A、B、C的含量,并与杂质对照品法测得的结果进行比较。结果: 瑞格列奈杂质A、B、C的相对保留时间分别为0.10、0.35、0.48,校正因子分别为0.65、0.76、3.06。检出限分别为0.27、0.12、4.21 ng,定量限分别为0.8、0.4、12.2 ng。采用校正因子的主成分自身对照法和外标法测得的结果无显著性差异。结论: 本方法经方法验证,可准确测定复方片剂中瑞格列奈3种杂质的含量。

Objective: To establish a self-contract method of principle componentusing the correction factor for the determination of repaglinide related substance in compound tablets. Methods: The assay was carried out on a C₁₈ column (250 mm×4.6 mm, 5μm) with the mobile phase consisting of 30 mmol·L^-1 potassium dihydrogen phosphate (adjusted to pH 3.2 with phosphate acid)and acetonitrile pumped at a flow rate of 1.5 mL·min^-1. The detection was carried out at 240 nm and a column temperature of 40℃. The injection volume was 20 μL.The slope of linear equation was used to determine the correction factor between impurities A, B, C and repaglinide. The relative retention time was used to determine the position of impurities. The developed method wasvalidated. The results obtained by the proposed method were compared with those by using the reference standards of impurities to verify the method accuracy. Results: The relative retention time between impurities A, B, C and repaglinide was 0.10, 0.35, and 0.48. The correction factor of impurities A, B, C was 0.65, 0.76, and 3.06. The limits of detection and quantification were found to be 0.27, 0.12, 4.21 ng and 0.8, 0.4, 12.2 ng for impurities A, B, C, respectively.There were no significant differences in the results determined by the external standard method and by the self-contrast and correction factor method. Conclusion: The method was simple, efficient and accurate for analyzing the three impurities of repaglinide in compound tablets.

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