复方醋酸甲地孕酮片有关物质测定方法的建立

目的: 建立复方醋酸甲地孕酮片有关物质测定方法。方法: 采用LC-MS-UV联用技术对复方醋酸甲地孕酮片中最大杂质(杂质B)和次大杂质(杂质A)进行结构确证，并采用HPLC法对其定量，对其他杂质按自身对照法计算。采用Agela Vensuil XBP C₁₈(L)色谱柱(4.6 mm×250 mm，5 μm)，流动相：乙腈-水(50∶50)，流速：1.0 mL·min^-1，检测波长：243 nm(杂质A、杂质B)，291 nm(其他杂质)，柱温：30℃，进样量：20 μL。结果: 杂质A和杂质B的浓度分别在0.308~10.28 μg·mL^-1和1.137~113.7 μg·mL^-1范围内线性关系良好，相关系数(n=5)均为1.000，平均回收率分别为101.9%和99.6%(n=9)，RSD为0.83%和1.1%(n=3)，最低检出限分别为0.5 ng和1.1 ng。结论: 所建立的方法简便、快速，可准确测定该制剂中杂质含量。

Objective: To establish a method for the determination of the related substances of compound megestrol acetate tablets. Methods: The structures of the maximum impurity(impurity B)and secondary maximum impurity(impurity A)were confirmed by LC-MS and the contents of the two impurities were quantified by HPLC.Other impurities were calculated by the main component self-contrasted method.An Agela Venusil XBP C₁₈(L)(4.6 mm×250 mm,5μm)was used with a mobile phase of acetonitrile - water(50∶50).The flow rate was 1.0 mL·min^-1,the detection wavelengths were 243 nm for impurity A and impurity B,and 291 nm for other impurities.The column temperature was 30℃,and the volume of injection was 20 μL. Results: Good linear correlations of impurity A and impurity B were observed within the ranges of 0.308 - 10.28 μg·mL^-1 and 1.137 - 113.7 μg·mL^-1(r=1.000)(n=5);the average recovery rates were 101.9% and 99.6%(n=9),respectively.The RSDs were 0.83% and 1.1%(n=3).The limits of detection were 0.5 ng and 1.1 ng,respectively.Conclusion: The method is simple,rapid,and accurate for determination of impurity content in preparation of compound megestrol acetate tablets.

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