阿瑞匹坦中有关物质检查方法的研究

目的:建立高效液相色谱法测定阿瑞匹坦原料药中的有关物质。方法: 采用Inertsil C₈色谱柱,以乙腈-水-三氟乙酸(50:50:0.05)为流动相,检测波长为215 nm。结果: 在选定的条件下,阿瑞匹坦与八种可能存在的杂质分离良好;阿瑞匹坦、起始物1、起始物2、中间体1、中间体2、脱氟阿瑞匹坦、SRS异构体、RRR异构体和RSS异构体的检测限分别为0.10、0.74、0.50、0.48、0.49、0.50、1.79和0.93 ng;阿瑞匹坦进样量在2~200 ng范围内,起始物1、起始物2、中间体1、中间体2、脱氟阿瑞匹坦、SRS异构体、RRR异构体和RSS异构体进样量在2~40 ng范围内,峰面积与进样量呈良好的线性关系;以阿瑞匹坦为参比,测得起始物1、起始物2、中间体1、中间体2、脱氟阿瑞匹坦、SRS异构体、RRR异构体和RSS异构体的校正因子分别为0.5、1.2、1.5、1.1、0.9、0.9、1.0和0.9。结论: 本法简便、专属、准确,可用于阿瑞匹坦原料药中有关物质的检查。关键字: 阿瑞匹坦;起始物;中间体;异构体;杂质分析;高效液相色谱法

Objective: To establish an HPLC method to determine the related substances of aprepitant. Methods: The HPLC method was performed on an Inertsil C₈ column with the mobile phase of acetonitrile-water-trifluoroacetic acid(50:50:0.05),the detection wavelength was set at 215 nm. Results: Under the selected chromatographic condition,aprepitant was completely separated from eight impurities that were potentially present.The LODs of aprepitant,initiator 1,initator 2,intermidate 1,intermidate 2,defluorinated aprepitant,SRS isomer,RRR isomer and RSS isomer were 0.10 ng,0.74 ng,0.50 ng,0.48 ng,0.49 ng,0.50 ng,1.79 ng and 0.93 ng,respectively.The linear range of aprepitant was 2-200 ng,and the linear ranges of initiator 1,initator 2,intermidate 1,intermidate 2,defluorinated aprepitant,SRS isomer,RRR isomer and RSS isomer were 2-40 ng.The correction factors of the initiator 1,initator 2,intermidate 1,intermidate 2,defluorinated aprepitant,SRS isomer,RRR isomer and RSS isomer were 0.5,1.2,1.5,1.1,0.9,0.9,1.0 and 0.9,respectively. Conclusion: The method is simple,specific,accurate and suitable for analyzing the related substances in aprepitant.

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