苯甲酸阿格列汀二甲双胍片中阿格列汀相关杂质的控制

Control of alogliptin related impurities in alogliptin benzoate and metformin hydrochloride tablets

目的开发了一种专属性强且高效的高效液相方法,用于分离和定量测定苯甲酸阿格列汀二甲双胍片中阿格列汀相关的杂质。方法首先根据苯甲酸阿格列汀的合成路径及可能的降解途径分析了复方片中可能存在的杂质,依据《中国药典》及ICH Q2中杂质方法开发等指导原则,进行了其中8种杂质的高效液相色谱条件的选择、优化以及全面的方法验证,最终使用0.05%三氟乙酸水溶液(取三氟乙酸0.5 mL,加水1000 mL溶解)为流动相A,0.05%三氟乙酸乙腈溶液(取三氟乙酸0.5 mL,加乙腈1000 mL溶解)为流动相B,以氰基硅烷键合硅胶为填充剂(Agilent SB CN,250 mm×4.6 mm,5μm),采用梯度洗脱模式进行杂质的分离、分析。结果该方法重现性好,精密度高,可以应用于产品生产质量控制。结论本品杂质控制方法的研究,为后续含有苯甲酸阿格列汀的复方产品提供一种有效的质量控制手段。

Objective To develop a highly specific and efficient high-performance liquid phase method for the separation and quantitative determination of alogliptin-related impurities in alogliptin benzoate and metformin hydrochloride tablets.Method Firstly,the possible impurities in the compound tablets were analyzed according to the synthesis route and possible degradation route of alogliptin benzoate.According to the guidelines for impurity method development in the ChP and ICH Q2,the selection,optimization and comprehensive method verification of HPLC conditions for 8 impurities were carried out.The 0.05%trifluoroacetic acid aqueous solution(take 0.5 mL trifluoroacetic acid,add 1000 mL of water to dissolve)was used as mobile phase A,and 0.05%trifluoroacetic acid acetonitrile Solution(take 0.5 mL of trifluoroacetic acid and dissolve in 1000 mL of acetonitrile)was used as mobile phase B by using cyanosilane bonded silica as a filler(Agilent ZORBAX SB CN,250 mm×4.6 mm,5μm).The separation and analysis of impurities was carried out using gradient elution mode.Result The method had the good reproducibility and high precision,and can be applied to product quality control.Conclusion The study on the impurity control method of this product provides an effective quality control method for fixed-dose combination containing alogliptin benzoate.