枸橼酸氯米芬反式异构体及有关物质检测方法的比较

Comparison of the methods of content determination of Z-isomer and related substances in clomifene citrate

目的:比较并讨论美国药典(USP)和中国药典(ChP)中枸橼酸氯米芬反式异构体及有关物质的检测方法。方法:对USP 和 ChP 中枸橼酸氯米芬的分析方法进行了比较,USP 方法为:色谱柱为 Modulo-Cart Qs Inertsil C_4柱(100 mm×4.6 mm,5μm);流动相为甲醇-水-三乙胺(50:50:0.3),用磷酸调 pH 为2.5;检测波长为233 nm 和290 nm;ChP 方法为:资生堂SG120A 硅胶柱(150 mm×4.6 mm,5μm);流动相:正己烷-三氯甲烷-三乙胺(80:20:1);检测波长:302 nm。结果:中美药典方法对反式异构体的检查结果均符合规定,中国药典方法所测结果略高;按美国药典方法可检出3个杂质,中国药典法只检出1个杂质。结论:中国药典中对于枸橼酸氯米芬有关物质的控制方法有待进一步完善,可借签别国药典方法作为中国药典方法的补充,从而更好地控制枸橼酸氯米芬的质量。

Objective：Different HPLC methods in USP and ChP of the content control of Z - isomer and related substances in clomifene citrate were compared and discussed. Method：The USP as well as ChP methods of clomifene analysis were compared in this paper. In the USP method, a Modulo - Cart QS Inertsil C4 （ 100 mm ×4.6mm,5μm）column was used,with a mixture of methanol, water, and triethylamine （50：50：0. 3 ） as mobile phase, adjusting with phosphoric acid to a pH of 2.5 as mobile phase and detected at 233 nm and 290 nm. In the ChP, a SHISEIDO SILICA SG120 （150 mm ×4.6mm,5μm）was used, with a mixture of hexane, chloroform and triethylamine（80： 20：1 ）as mobile phase, and detected at 302 nm. Result：The content of Z -isomer meet the requirement while the result was higher with ChP method than that of USP method. Three impurities were found with USP method ,and only one was found with ChP method. Conclusion ：The ChP method for control of the related substances in clomifene citrate can be further perfected. The USP as well as BP method can be the complement for the ChP method and used for control the quality of clomifene citrate.