A novel ultra‐performance liquid chromatographic (UPLC) method has been developed and approved for the quantitative determination of enzalutamide (ENZ) and its impurities in drug product dosage form by applying the quality by design with design of experiments approach. An efficient chromatographic separation was achieved on a Waters ACQUITY CSH C₁₈ (100 × 2.1 mm × 1.7 μm) column in gradient elution mode. A mixture of potassium phosphate monobasic buffer and acetonitrile (10 mm, adjusted to pH 4.0 with 1% orthophosphoric acid) at a flow rate of 0.2 mL min⁻¹ (column temperature at 40°C) under ultraviolet detection at 270 nm was used for quantitation. The peak resolution among ENZ and its impurities (Impurity‐1, Impurity‐2, Impurity‐3, Impurity‐4, Impurity‐5, Impurity‐6 and Impurity‐7) was greater than 2.5. Regression analysis confers an R² value (correlation coefficient) higher than 0.999 for the active substance and impurities. The detection level for ENZ impurities was at a level below 0.015% (0.12 μg/mL). The accuracy levels for different compounds were close to 100%. The inter‐ and intra‐day precisions for ENZ and impurities were evaluated and their relative standard deviation (%) values were less than 3.5. Our results show that the UPLC–UV stability‐indicating method will be an essential tool that could determine the drug product’s impurities and be useful in regular quality control and stability studies of the ENZ drug product dosage form.

中文翻译：

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通过设计和实验方法来设计质量，用于开发软凝胶剂型制剂中恩杂鲁胺及其杂质的稳定性指示LC方法

新型超高效液相色谱（UPLC）方法已经开发出来，并已批准通过设计和实验方法设计质量保证方法来定量测定药物剂型中的恩杂鲁胺（ENZ）及其杂质。在Waters ACQUITY CSH C ₁₈（100×2.1 mm×1.7μm）色谱柱上以梯度洗脱模式实现了有效的色谱分离。磷酸钾一元缓冲液和乙腈的混合物（10 m m，用1％正磷酸调节至pH 4.0），流速为0.2 mL min ^-1在270nm的紫外线检测下（40℃的柱温）进行定量。ENZ及其杂质（杂质1，杂质2，杂质3，杂质4，杂质5，杂质6和杂质7）的峰分辨率大于2.5。回归分析赋予R ²活性物质和杂质的值（相关系数）高于0.999。ENZ杂质的检测水平低于0.015％（0.12μg/ mL）。不同化合物的准确度水平接近100％。评估了ENZ和杂质的日间和日内精度，它们的相对标准偏差（％）值小于3.5。我们的结果表明，UPLC-UV稳定性指示方法将是确定药物杂质的必不可少的工具，可用于ENZ药物剂型的常规质量控制和稳定性研究。