HPLC法测定不同来源米非司酮胶囊的有关物质

目的：建立米非司酮胶囊有关物质测定的HPLC法，对其主要有关物质进行研究，制定有关物质合理限度，有效控制产品质量。方法：采用RP-HPLC法，色谱柱为C₁₈柱，流动相：乙腈-10 mmol·L^-1磷酸二氢钾溶液（用磷酸调节pH至2.5）（35：65），流速1.0 mL·min^-1，检测波长304 nm，柱温35 ℃。结果：米非司酮胶囊中的主要杂质为N-单去甲基米非司酮，既是副产物也是降解产物。A企业3批样品中该杂质含量均为0.5%，B企业3批样品中该杂质含量均为0.2%。A企业3批样品杂质总量为0.6%~0.7%，B企业3批样品杂质总量为0.2%~0.3%。结论：本方法可快速有效分离米非司酮胶囊中各有关物质。对已知、未知有关物质分别设定不同限度，可有效控制该药品质量。

Objective: To establish an HPLC method for the determination of related substances in mifepristone capsules,and to study its principal related substances and set reasonable limits for related substances to improve the quality control for mifepristone capsules. Methods: Related substances were analyzed by the RP-HPLC method.The C₁₈ column was used and a mixture of acetonitrile and phosphate BS(10 mmol·L^-1 potassium dihydrogen phosphate,adjusted to pH 2.5 with phosphoric acid)(35:65) was used as the mobile phase.The flow rate was 1.0 mL· min^-1,and the detection wavelength was 304 nm,and the column temperature was 35 ℃. Results: The main impurity was N-mono-demethylated mifepristone,which was both a by-product and a degradation product.The content of this impurity in 3 batches of manufacturer A was 0.5%,and that in 3 batches of manufacturer B was 0.2%.The total content of impurities in 3 batches of manufacturer A was 0.6%-0.7%,and in 3 batches of manufacturer B was 0.2%-0.3%. Conclusion: Mifepristone and its related substances were obviously separated under the chromatographic system described above.The limit for N-mono-demethylated mifepristone was 1.0% and the limit for other individual impurities was 0.2% and the limit for total impurities was 1.5%.This method can control the quality of mifepristone capsules effectively.