药品杂质遗传毒性评价的概述

Review on the Evaluation of Genotoxcity for Drug Impurities

本文综述了近年来国内外药品杂质遗传毒性评价的进展。药品遗传毒性评价的结果直接关系到药品杂质限度的制定,各种杂质的遗传毒性评价方法的研究进展迅猛,在现阶段条件下,使用计算机预测药品杂质的遗传毒性;探索以γH2AX为代表的生物标志物检测替代传统的体内外遗传毒性检测体系;并使用斑马鱼模式动物对其遗传毒性进行验证是行之有效的杂质遗传毒性评价策略。建立从计算机预测(in silico)、体外生物标志物(in vitro)到体内验证(in vivo)的药品杂质遗传毒性评价平台,有助于建立科学的杂质控制标准,提高药品质量的科学性,药品杂质遗传毒性评价水平的提升对于建设药品关键质量属性评价平台水平意义重大。

This article reviews the progress in the evaluation of genetic toxicity of pharmaceutical impurities in recent years.The results of drug genotoxcity evaluation are of great significance to the formulation of drug impurity limits.The research on the genotoxcity evaluation methods of various impurities is progressing rapidly.Under the current conditions,it is an effective impurity genotoxcity evaluation strategy that the computer is used to predict the genotoxcity of drug impurities;while theγH2AX biomarker testing method is explored to replace the traditional and genotoxcity testing system;and then zebrafish model animals are used to verify its genotoxcity.Establishing a platform for evaluating the genotoxcity of drug impurities from computer prediction,in vitro biomarkers to verification will help establish scientific impurity control standards and improve the scientific nature of drug quality.The improvement of the evaluation level of impurity genotoxcity is of great significance to the construction of a technical evaluation platform for key quality attributes of drugs.