摘要
目的:对亮菌甲素注射剂杂质谱进行研究。方法:采用液质联用技术对注射用亮菌甲素和亮菌甲素注射液中有关物质的结构进行解析,结合强制降解试验,推测各杂质的来源,并利用ADMET Predictor软件预测各杂质毒性。结果:亮菌甲素与相邻杂质及各杂质之间分离良好。推测了亮菌甲素注射剂杂质谱中10个杂质的结构,其中杂质1~5来源于碱降解,杂质6、杂质7来源于光降解,杂质8为原料引入,杂质9、杂质10为亮菌甲素与辅料丙二醇反应的产物。软件预测结果显示,亮菌甲素、杂质8的预测毒性很低,风险低;其他杂质可能具有一定的潜致敏性、染色体畸变、生殖毒和肝脏不良反应。结论:通过对亮菌甲素注射剂杂质谱研究,推测了杂质的结构、来源及其毒性,为其生产工艺和质量控制提供依据。
Objective:To study the impurity profile of Armillarisin A Injections.Methods:The impurities of Armillarisin A for Injection and Armillarisin A Injections were analyzed by LC-MS,the source of each impurity was predicted by forced degradation tests,and the toxicities of each impurity were speculated by the ADMET Predictor software.Results:Armillarisin A and all impurities were well separated.The structures of 10 impurities in the impurity profile of Armillarisin A Injections were identified,among which,impurities 1-5 were derived from alkaline degradation,impurity 6 and 7 were derived from light degradation,impurity 8 was from raw materials,impurity 9 and 10 were reaction products of Armillarisin A and auxiliary material propanediol.The software predicted that the toxicities of Armillarisin A and impurity 8 were very low and the risks were low;other impurities might have certain toxicities,such as potential sensitization,chromosomal aberration,reproductive toxicity and/or liver adverse reactions.Conclusion:The impurity profile of Armillarisin A injections clarifies the structures,sources and toxicities of the impurities.It can provide references for production process and quality control of Armillarisin A Injections.
作者
尹菁
薛敏华
康丽洁
石蓓佳
陆益红
YIN Jing;XUE Minhua;KANG Lijie;SHI Beijia;LU Yihong*(Jiangsu Institute for Food and Drug Control,Nanjing 210019,China;Fu Yang Fifth People's Hospital,Fuyang,Anhui 236063,China)
出处
《药学与临床研究》
2022年第1期19-24,共6页
Pharmaceutical and Clinical Research
作者简介
尹菁,女,副主任药师,E-mail:maple8275@163.com;通讯作者:陆益红,女,主任药师,E-mail:yihonglu@163.com。
