HPLC法测定阿托伐他汀钙有关物质

目的：建立阿托伐他汀钙有关物质测定方法。方法：采用HPLC法，已知杂质采用对照品法定性和定量，其他杂质采用自身对照法计算。采用Wondasil C₁₈色谱柱（4.6 mm×250 mm，5 μm），以乙腈-四氢呋喃-醋酸铵缓冲液为流动相，梯度洗脱，流速1.0 mL·min^-1，检测波长244 nm，柱温30 ℃，进样量20 μL。结果：阿托伐他汀与相邻杂质（杂质B和杂质C）及各已知杂质之间的分离度均大于1.5；杂质A、B、C、D、E的定量限分别为30、40、40、20、10 ng，且在各自的线性范围内线性关系良好（r> 0.9901，n=5）；平均回收率（n=9）分别为98.5%、111.3%、91.5%、106.6%、106.5%，RSD分别为4.8%、4.1%、4.7%、7.3%、6.4%。结论：本法经方法学验证，可测定阿托伐他汀钙中的有关物质。

Objective: To establish a method for the determination of the related substances of atorvastatin calcium. Methods: An optimal HPLC method was set up.The known impurities were qualified and quantified by standard method.Other impurities were calculated by the main component self-contrasted method.A Wondasil C₁₈ column (4.6 mm×250 mm,5 μm) was applied.The mobile phase was acetonitrile-tetrahydrofuran-ammonium acetate buffer with a gradient elution at a flow rate of 1.0 mL· min^-1 and the detection wavelength was set at 244 nm.The column temperature was 30 ℃,and the volume of injection was 20 μL. Results: The resolutions between atorvastatin and adjacent impurities(impurities B and C),and between the known impurities were greater than 1.5.The limits of quantification of impurities A,B,C,D,E were 30,40,40,20,10 ng.The calibration curves of five known impurities were linear in the self-concentration range(r> 0.9901,n=5).The average recovery rates(n=9) were 98.5%,111.3%,91.5%,106.6%,106.5%;RSDs were 4.8%,4.1%,4.7%,7.3%,6.4%. Conclusion: The method is reproducible and accurate for determination of the related substances in atorvastatin calcium according to methodology validation.

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