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.
JIANG Hui-yuan, WANG Yan-ni, CAO Min, NIU Xiao-shu, LI Jin
. Research on determination of amoxicillin polymers by RP-HPLC method replacement of size-exclusion chromatography method*[J]. Chinese Journal of Pharmaceutical Analysis, 2023
, 43(5)
: 817
-826
.
DOI: 10.16155/j.0254-1793.2023.05.12
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