目的: 对比分析分子排阻Sephadex G-10方法(以下简称G-10法)和RP-HPLC方法检测阿莫西林中聚合物杂质的准确性,探讨RP-HPLC法替代G-10法检测阿莫西林聚合物的可行性。方法: 采用溶液稳定性考察方法,考察和对比2种方法中聚合物含量的变化情况及影响因素;分别采用2种方法测定43批阿莫西林产品中聚合物杂质的含量,并对2种检测方法的结果进行相关性分析和多元线性回归,探索2种方法检测结果的关系。结果: 阿莫西林杂质J(n=1)为阿莫西林产品中含量最大的聚合物杂质,各聚合物在室温下相对稳定,但温度升高可加速各聚合物的生成,其中杂质J(n=1)增加速度最快,其次为杂质K、杂质L和杂质J(n=2);SPSS软件分析2种方法检测结果发现,G-10方法检出的阿莫西林聚合物含量与RP-HPLC方法检出的杂质L、杂质J(n=1)和杂质J(n=2)含量相关性显著;建立多元线性回归模型得到方程:Y=0.136X1-0.241X2+1.915X3+0.006。结论: 建议在有关物质项下优化杂质K、杂质L、杂质J(n=1)和杂质J(n=2)的限度替代阿莫西林聚合物检测。
Objective: To compare and analyze accuracy of amoxicillin polymers detection between size-exclusion chromatography method of Sephadex G-10 (G-10 method) and RP-HPLC method, and discussion on possibility of amoxicillin polymer detection by RP-HPLC method replacement of G-10 method. Methods: Comparative study of amoxicillin polymers content changes and influencing factors between two detection methods by solution stability investigation, two detection methods were used to detect the polymers content in 43 batches of amoxicillin. Meanwhile, correlation analysis and multiple linear regression were performed based on the results of the two detection methods to explore their relationship. Results: Amoxicillin impurity J (n=1) was the most abundant polymer impurity in amoxicillin products. The polymer impurities were relatively stable at room temperature, but the increase of temperature could accelerate the formation of polymers. As a result, the impurity J (n=1) increased the fastest, followed by impurity K, impurity L and impurity J (n=2). SPSS software was used to analyze the results of the two methods. It was found that the content of amoxicillin polymer detected by G-10 method was significantly correlated with the contents of impurity L, J(n=1) and J(n=2) detected by RP-HPLC method. Multiple linear regression model was established by the equation: Y=0.136X1-0.241X2+1.915X3+0.006. Conclusion: It is feasible to cancel amoxicillin polymer detection by G-10 method, and it is suggested to add the limits of impurity K, impurity L, impurity J (n=1) and impurity J (n=2) under relevant substances detection to replace the detection of amoxicillin polymer.
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