Objective:This study was conducted to investigate the genotoxicity of known impurities in clozoxazone in vitro,and to provide evidence for clinical drug safety.Methods:The methods of Derek and Sarah were used to classify and evaluate clozoxazone impurities from the aspect of quantitative structure-activity relationship(Q)SAR.Reverse mutation were further used to verify those impurities predicted as positive.Results:Impurity 6 and impurity 7 were predicted by Derek and Sarah methods as positive.In the bacterial reverse-mutation tests of five strains,the results of impurity 6 and impurity 7 were negative,their numbers of reverse mutation colonies did not exceed twice those number of spontaneous reverse-muta-tion colonies,in the dose range of 15-1250 μg/plate with or without S9.Conclusion:Clozoxazone impurity 6 and impurity 7 are negative candidates of bacterial reverse mutation,and can be controlled as non-geno-toxic impurities.
维普
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