双氯芬酸缓释胶囊与片剂的杂质谱研究  

Impurity profiling study of diclofenac delayed-release capsules and tablets

作　　者：王铁松[1] 车宝泉[1] 冯文化[2] 施捷[1] 纪菁[1] 金鑫[1] 王威[1] 胡琴[1] 

机构地区：[1]北京市药品检验所中药成分分析与生物评价北京市重点实验室,北京100035 [2]中国医学科学院药物研究所,北京100050

出　　处：《药物分析杂志》2015年第5期910-914,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：北京市科技计划资助项目(编号Z131100005613032)

摘　　要：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 po- tassium 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 prewntion and control measures were proposed according to the causes of impurity formation. Results：Diclofenac formulations were easily degradable, and the main degrada- tion 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.

关 键 词：双氯芬酸钠 双氯芬酸钾 有关物质 杂质谱检测 杂质定向合成 IC50细胞毒性评价 基因毒性 杂质结构确证 杂质溯源分析 防控措施 

分 类 号：R917[医药卫生—药物分析学]