Abstract: Objective To study the acute toxicity in mice and cytotoxicities of the impurities of Ondansetron. Methods pre-experiment to determine the initial dose, the mice were grouped randomly(half male and half female, 20 mice per group) in the formal experiment. The animal reactions and death were recorded for 14 days. The cytotoxicities on fibroblasts(L929), canine kidney cells(MDCK) and human umbilical vein endothelial cells(HUVEC) were measured. Results The LD50 and 95% confidence limit of the impurity 1 of Ondansetron(intragastric administration) was 1798.8± 178.2 mg ·kg-1, no apparent damage was discovered in the anatomy of the viscera. The LD50 and 95% confidence limit of the impurity 2 of Ondansetron injected intravenously in mice was 49.63± 7.63 mg ·kg-1, shortness of breath and convulsions were shown after intravenous injection and gradually ease, no apparent damage was shown in the anatomy of the viscera. The impurity 3 of Ondansetron was adminstrated intragastriclly to mice 2 000 mg ·kg-1 daily for 3 days, all mice was survived and no toxicity reactions were shown during the observed period． The purity 1,2, and 3 all significantly decreased the viability of L929 cells(P < 0.05). The impurity 3 of Ondansetron significantly promoted the proliferation of HUVEC(P < 0.05). Conclusion The impurity 1 and 2 of Ondansetron had certain toxicity to mice and cells. The toxicity of the impurity 3 of Ondansetron is low. The data can provide the experimental basis to establish the quality standards of Ondansetron, and improve the safety of clinic use.

Key words: ondansetron, mice acute toxicity, cytotoxicity