基因毒性杂质的毒理学评估策略

Toxicological evaluation strategy of genotoxic impurities

基因毒性杂质的限度确定是药物安全研究的重要内容。有潜在基因毒性的杂质根据其结构特征和毒理学数据可分为5类:已知有致突变性及致癌性的杂质、有致突变性但致癌性未知的杂质、含有与药物活性成分结构无关的警示结构但无致突变性数据的杂质、含与药物活性成分相关警示结构的杂质以及致癌风险高的特殊杂质。本文以毒理学评价的方法,分类对基因毒性杂质的评估策略进行综述,并示例杂质限度确定的方法。

The determination of acceptable limits for genotoxic impurities is an important part of drug safety research. Impurities with potential genotoxicity can be divided into five categories according to their structural characteristics and toxicological data: known mutagenic carcinogens,known mutagens with unknown carcinogenic potential,substances containing alerting structure that are unrelated to the structure of the drug substance but without mutagenicity data,substances containing alerting structure related to the drug substance and special impurities with high carcinogenic potency. This paper uses the method of toxicological evaluation to review the evaluation strategies of genotoxic impurities,and illustrate the method for determining acceptable limits.