氯解磷定注射液的杂质谱  

Impurity profiling study on pralidoxime chloride injection

作　　者：吴兆伟[1,2] 黄晓君[2] 王铁松[2] 胡琴[2] 吴斌[2] 赵怀清[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]北京市药品检验所化学室,北京102206

出　　处：《沈阳药科大学学报》2016年第11期876-882,共7页Journal of Shenyang Pharmaceutical University

基　　金：北京市科技计划项目(Z131100005613032)

摘　　要：目的研究氯解磷定注射液的杂质谱。方法用高效液相色谱对2家企业41批样品进行杂质定量检测,根据液-质联用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分别测定校正因子。对已获得对照品的杂质进行IC50细胞毒性评价。结果氯解磷定注射液的主要降解杂质为杂质A、C和F(氯解磷定的Z型异构体),其中杂质A的IC50值约为主成分的1/3,需重点检测和控制。结论通过对氯解磷定注射液杂质谱的研究,确定了氯解磷定的8个杂质并分析了杂质的来源与毒性,为质量控制提供参考。Objective To study the impurity profiling of pralidoxime chloride injection. Methods The liquid chromatography was used for impurity detection and the structure of impurities was confirmed with HPLC- MS analysis and oriented synthesis. The mass balance method was used to mark the reference standards of impurities and the IC50 cell toxicity evaluation were conducted. Further experiments and comprehensive analyses were made to infer sources of impurities in 41 batches of samples from 2 manufacturers. Results The main degradation products in pralidoxime chloride injection were impurities A, C and the F（Z-isomer）. The toxicity of impurities A made it to be the key target of detection and control. Conclusions By analyzing the source of impurities through the study on the impurity profiles of pralidoxime chloride injection, the impurities can be controlled, which provides reference for the quality control of pralidoxime chloride injection.

关 键 词：氯解磷定 氯解磷定注射液 有关物质 杂质谱检测 杂质定向合成 IC50细胞毒性评价 杂质结构确证 

分 类 号：R917[医药卫生—药物分析学]