双氯芬酸缓释胶囊与片剂的杂质谱研究

目的:研究双氯芬酸钠缓释胶囊剂和双氯芬酸钾片剂的杂质谱。方法: 用液相色谱进行杂质检测分析,根据液质分析和定向合成确证杂质结构,采用质量平衡法标化杂质对照品,并进行IC₅₀细胞毒性评价和基因毒性预测;通过对19家企业170批样品的进一步实验与综合分析推断杂质的来源,并根据杂质形成的原因提出针对性防控措施。结果: 双氯芬酸钠和双氯芬酸钾制剂易降解,其中杂质B、C毒性高,需重点检测和控制。结论: 双氯芬酸制剂易受水分和光照等因素影响而降解,不同企业药品的杂质水平存在较大差异,可通过一系列措施提高药品质量。

Objective: To study impurity profiling of diclofenac sodium delayed-release capsules and diclofenac potassium tablets. Methods: The liquid chromatography was used for impurity detection and the structure of impurities was confirmed with liquid chromatographic analysis and oriented synthesis.The mass balance method was used to mark the reference standards of impurities and the IC₅₀ cell toxicity evaluation and the genetic toxicity prediction were conducted.Further experiments and comprehensive analyses were made to infer sources of impurities in 170 batches of samples from 19 manufacturers and the specific prevention and control measures were proposed according to the causes of impurity formation. Results: Diclofenac formulations were easily degradable, and the main degradation impurities B and C were highly toxic, which were the key targets of detection and control. Conclusion: Quality of diclofenac formulations are easily degraded due to light and water, and the content of impurities in formulations from different manufacturers differs a lot.A series of countermeasures should be carried out to improve the quality.

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