A quality by design-based stability indicating HPLC method has been developed for hydroxychloroquine sulfate impurities. The optimized HPLC method can detect and quantify the hydroxychloroquine sulfate and related organic impurities in pharmaceutical solid oral dosage forms. Nowadays, for the quantification of impurities in drug products demands more comprehensive way of analytical method development. The quality by design approach allows the assessment of different analytical parameters and their effects with minimum number of experiments. A highly sensitive and stability indicating RP-HPLC method was developed and evaluated the risk assessment prior to method validation. The chromatographic separation was achieved with X-terra phenyl column (250 × 4.6 mm, 5 µm) using phosphate buffer (0.3 M and pH 2.5). The gradient method flow rate was 1.5 mL min−1 and UV detection was made at 220 nm. The calibration curve of hydroxychloroquine sulfate and related impurities were linear from LOQ to 150% and correlation coefficient was found more than 0.999. The precision and intermediate precision % RSD values were found less than 2.0. In all forced degradation conditions, the purity angle of HCQ was found less than purity threshold. The optimized method found to be specific, accurate, rugged, and robust for determination of hydroxychloroquine sulfate impurities in the solid oral dosage forms. Finally, the method was applied successfully in quality control lab for stability analysis.

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用于治疗 COVID-19 的硫酸羟氯喹杂质的稳定性指示 LC 方法开发以及在方法验证之前通过质量源于设计方法进行风险评估

针对硫酸羟氯喹杂质，开发了一种基于设计的质量稳定性指示 HPLC 方法。优化的HPLC方法可以对药物固体口服剂型中的硫酸羟氯喹及相关有机杂质进行检测和定量。如今，药品中杂质的定量需要更全面的分析方法开发。质量源于设计方法允许以最少的实验次数评估不同的分析参数及其效果。开发了一种高度灵敏和稳定的 RP-HPLC 方法，并在方法验证之前进行了风险评估。使用 X-terra 苯基柱 (250 × 4.6 mm, 5 µm) 使用磷酸盐缓冲液（0.3 M 和 pH 2.5）实现色谱分离。梯度法流速为 1.5 mL min−1，UV 检测在 220 nm 处进行。硫酸羟氯喹及相关杂质的校准曲线从LOQ到150%呈线性，相关系数大于0.999。精密度和中间精密度% RSD 值小于 2.0。在所有强制降解条件下，HCQ 的纯度角均小于纯度阈值。该优化方法对于测定固体口服剂型中的硫酸羟氯喹杂质而言是特异、准确、稳定且稳健的。最后，该方法成功应用于质量控制实验室进行稳定性分析。