奥美拉唑杂质毒性预测及细胞毒性研究  

Toxicity Prediction and Cytotoxicity Studies of Omeprazole Impurities

作　　者：刘荷英 刘波 郑洋滨 陈涛 刘宁 LIU Heying;LIU Bo;ZHENG Yangbin;CHEN Tao;LIU Ning(Jiangxi Institute for Drug Control,NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine,Jiangxi Province Engineering Research Center of Drug and Medical Device Quality,Nanchang Jiangxi 330029,China;Shanghai PharmoGo Co.,Ltd,Shanghai 200127,China)

机构地区：[1]江西省药品检验检测研究院,国家药品监督管理局中成药质量评价重点实验室,江西省药品与医疗器械质量工程技术研究中心,江西南昌330029 [2]上海凡默谷信息技术有限公司,上海200127

出　　处：《药品评价》2023年第9期1054-1059,共6页Drug Evaluation

基　　金：江西省药品监督管理局科研项目(2019JS09)

摘　　要：目的通过基于定量结构-性质关系(QSPR)模型的毒性预测和细胞毒性试验研究,多方面评价奥美拉唑相关杂质的毒性。方法采用ADMET Predictor软件对奥美拉唑及其16个相关杂质(杂质A~P)进行心脏毒性、大鼠急性毒性、致癌性、肝脏不良反应和致突变性预测,并按打分规则计算出毒性风险系数,以评价各杂质毒性大小,再采用MTT法对奥美拉唑钠及7种杂质(杂质A~E、J、K)进行L-929细胞毒性试验研究。结果4个杂质的毒性风险系数高于奥美拉唑,杂质A有致突变性和肝脏毒性,杂质C有大、小鼠致癌性,杂质F、G有致突变性。杂质B的细胞毒性比奥美拉唑钠大。结论通过软件毒性预测结合细胞毒性试验可多方面快速评价奥美拉唑杂质的安全性。Objective To evaluate the toxicity of omeprazole-related impurities by toxicity prediction using a software based the QSPR model and cytotoxicity test.Methods ADMET predictor software was used to predict the cardiotoxicity,acute toxicity in rats,carcinogenicity,liver side effects and mutagenicity of omeprazole and its sixteen impurities(impurity A~P),the toxicity risk coefficients were calculated according to the scoring rules to evaluate the toxicity of the impurities.Then the cytotoxicity of omeprazole sodium and seven impurities(impurity A~E,J,K)were studied by MTT method with L-929 cells.Results The toxicity risk coefficients of four impurities were higher than that of omeprazole.The impurityA had hepatotoxicity and mutagenicity,the impurity C had carcinogenicity for rats and mice,and the impurity F and G had mutagenicity.The cytotoxicity of impurity B was greater than that of omeprazole sodium.Conclusion The safety of omeprazole-relatedimpurities can be evaluated comprehensively and quickly by software toxicity prediction combined with cytotoxicity test.

关 键 词：奥美拉唑 杂质 毒性预测 细胞毒性 定量结构-性质关系(QSPR)模型 

分 类 号：R994.3[医药卫生—毒理学]