呋塞米杂质B的潜在毒性预测研究

Potential toxicity of impurity B in furosemide preparation

目的基于计算化学方法,研究呋塞米工艺路线中杂质B的潜在毒性。方法通过分子模拟方法,预测呋塞米工艺路线中杂质B可能影响的蛋白靶标,以及可能引起的毒副作用。结果预测发现,杂质B可能会与碳酸酐酶2、甲状腺素结合球蛋白和巨噬细胞抑制因子结合。该结果可能与呋塞米使用过程中的甲状腺功能亢进有关。结论分子模拟方法可用于研究药物制备过程中杂质的潜在靶标,进而预测其可能引起的毒副作用。

Objective To determine the potential toxicity of the impurity B in furosemide preparation with computation chemistry methods.Methods Target-proteins influenced by impurity were predicted with molecular modeling.Results Three proteins were identified as possible targets for impurity B:carbonic anhydraseⅡ,thyroxine-binding globulin and macrophage migration inhibitory factor.These results might be related to the hyperthyroidism of furosemide usage.Conclusion Molecular modeling helps predict the target of impurities,and evaluate the toxicity.