目的 对苹果酸舒尼替尼的3个已知杂质进行（定量）构效关系计算机模型［（Q）SAR］评价，并对杂质E进行细菌回复突变（Ames）试验研究。方法 根据国际人用药品注册技术协调会（ICH）M7指导原则的要求，采用基于专家知识规则的Derek和基于统计学的Sarah两类（Q）SAR评价系统，对苹果酸舒尼替尼的3个杂质——杂质v-7、杂质v-1及杂质E进行评价和分类。对于确定为遗传毒性阳性的杂质E，采用Ames试验进行验证。结果 苹果酸舒尼替尼的杂质v-7、杂质v-1预测结果为阴性，杂质E预测结果为阳性，且分类为3类。在加与不加S9的条件下，Ames试验中杂质E8～5000μg·皿^-1质量浓度回复突变菌落数均未超过溶剂对照组的2倍，试验结果为阴性。结论 苹果酸舒尼替尼的3个杂质——杂质v-7、杂质v-1及杂质E均可以按照非遗传毒性杂质进行控制。

Objective Three known impurities of Sunitinib malate were evaluated by (quantitative) structure-activity relationship computer model [(Q) SAR], and to study the impurity which was classified as class 3 by Ames test.Methods According to ICH M7 guidelines, two (Q)SAR prediction methodologies were applied(expert rule-based Derek and statistical-based Sarah) to assess and classify three impurities in Sunitinib malate (impurity v-7, impurity v-1 and impurity E). Ames test was used to verify impurity E which was confirmed as positive genotoxicity.Results (Q)SAR evaluation showed that impurity v-7 and impurity v-1 were nonmutagenic while impurity E was positive, which was classified as class 3. The results of Ames test indicated that the number of revertant colonies of test sample group was no more than twice of solvent control group induced revertant colonies and the test result represented negative at doses from 8 to 5 000 μg·plate^-1 with or without S9.Conclusion The three impurities of sunitinib malate --impurity v-7, impurity v-1 and impurity E can be controlled as non-genotoxic impurities.

R965.3