盐酸罗格列酮中杂质的ADMET毒性预测分析  

ADMET Toxicity Prediction Analysis of Impurities in Rosiglitazone Hydrochloride

作　　者：郑媛媛 杨烨 聂鹏 Zheng Yuanyuan;Yang Ye;Nie Peng(Pharmacology and Toxicology(Pharmaceutical Packaging Materials)Room,Guizhou Institute for Food and Drug Control,Guiyang 550004;Clinical laboratory Guizhou Electric Power Hospital,Guiyang 550004,China)

机构地区：[1]贵州省食品药品检验所药理毒理(药包材)室,贵州贵阳550004 [2]贵州电力医院检验科,贵州贵阳550004

出　　处：《广东化工》2023年第9期196-198,共3页Guangdong Chemical Industry

基　　金：黔科合基础(ZK[2021]一般041)。

摘　　要：目的:对盐酸罗格列酮的3种杂质进行毒性预测分析。方法:采用AI算法,通过来自文献和制药企业授权的数据,进行ADMET性质的毒性分析。结果:在内分泌毒性预测方面,杂质B可能会产生雌激素受体毒性;在过敏预测方面,三种杂质均可能会导致皮肤过敏反应,并且杂质A和杂质C可能会有呼吸过敏性;在基因毒性的预测方面,杂质A可能会导致培养的哺乳动物细胞染色体变异;在肝脏不良反应预测方面,三种杂质可引起γ-谷氨酰转肽酶水平升高,肝脏毒性可能性较大。结论:对3种杂质整体评价,ADMET风险系数均较低,提示风险较小,并且该三种杂质毒性打分均低于限度,毒性均较低,但杂质A可能具有基因毒性,需进一步深入研究。Objective:Three impurities of rosiglitazone hydrochloride were analyzed for toxicity prediction.Methods:Toxicity analysis of ADMET properties was performed using AI algorithms based on data from literature and pharmaceutical company authorizations.Results:In terms of endocrine toxicity prediction,impurity B may produce estrogen receptor toxicity;in terms of allergy prediction,all three impurities may cause skin anaphylaxis,and impurities A and C may have respiratory irritability;in the prediction of genotoxicity,impurity A may cause chromosomal variation in cultured mammalian cells;in the prediction of liver adverse reactions,three impurities can cause the increase ofγ-glutamyl transpeptidase level,and the possibility of liver toxicity is greater.Conclusion:For the evaluation of the three impurities,the coefficient of ADMET is low,indicating that the risk is small.The toxicity scores of the three impurities are lower than the limit,and the toxicity is low.However,impurity A may have genotoxicity,which requires further study.

关 键 词：盐酸罗格列酮 杂质 毒性预测 

分 类 号：R927.1[医药卫生—药学]