HPLC法测定(<i>E</i>)-4-2-(4-氯苯氧基)-2-甲基丙酰氧基-3-甲氧基苯基丙烯酸的有关物质

许静; 彭红; 熊贤招

doi:10.11665/j.issn.1000-5048.20200505

HPLC法测定(E)-4-2-(4-氯苯氧基)-2-甲基丙酰氧基-3-甲氧基苯基丙烯酸的有关物质

Determination of related substances in (E)-4-2-(4-chlorophenoxy)-2-methylpanoyloxy-3-methoxyphenyl acrylic acid by HPLC

摘要

摘要: 采用HPLC法分析（E）-4-［2-（4-氯苯氧基）-2-甲基丙酰氧基］-3-甲氧基苯基丙烯酸的有关物质，采用Ultimate XB-C₁₈色谱柱（4.6 mm×150 mm，5 μm），甲醇-1%乙酸水（70∶30）为流动相，检测波长为275 nm。结果显示，（E）-4-［2-（4-氯苯氧基）-2-甲基丙酰氧基］-3-甲氧基苯基丙烯酸与各中间体及强制破坏产生的降解产物均分离良好，3批原料药中杂质限量均小于0.1%，分离并鉴定了其主要杂质C，在0.20～59.96 μg/mL范围内，杂质C的质量浓度与峰面积呈良好的线性关系（r=0.999 9）。采用杂质对照品法和自身高低浓度对比法建立了（E）-4-［2-（4-氯苯氧基）-2-甲基丙酰氧基］-3-甲氧基苯基丙烯酸的有关物质控制方法。经方法学验证可用于（E）-4-［2-（4-氯苯氧基）-2-甲基丙酰氧基］-3-甲氧基苯基丙烯酸有关物质的检测。

Abstract: HPLC method was used for the determination of related substances in (E)-4-2-(4-chlorophenoxy)-2-methylpanoyloxy-3-methoxyphenyl acrylic acid. The separation was achieved by Ultimate XB-C₁₈ column (4.6 mm×150 mm,5 μm) with mobile phase composed of methanol-1% acetic acid water (70∶30) at a wavelength of 275 nm. The results showed that (E)-4-2-(4-chlorophenoxy)-2-methylpanoyloxy-3-methoxyphenyl acrylic acid with various intermediates and compulsory destruction of degradation products were well separated. The impurity limit in three batches of API was less than 0.1% and the main impurity C was isolated and identified. Within the range from 0.20 to 59.96 μg/mL, the mass concentration of impurity C has good linear relationship with the peak area (r=0.999 9). The control method of related substances for (E)-4-2-(4-chlorophenoxy)-2-methylpanoyloxy-3-methoxyphenyl acrylic acid was established by impurity reference method and self-high and low concentration comparison. Methodological validation can be used for the detection of related substances of (E)-4-2-(4-chlorophenoxy)-2-methylpanoyloxy-3-methoxyphenyl acrylic acid.

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