盐酸多西环素主要有关物质体外抗菌活性及毒性的研究

目的：比较盐酸多西环素与其主要有关物质体外抗菌活性及毒性，为制定该品种有关物质控制限度提供参考依据。方法：采用纸片扩散法和常量肉汤二倍稀释法考察盐酸多西环素主要有关物质的抗菌活性；采用中国仓鼠肺细胞（CHL）和斑马鱼动物模型评价其毒性。结果：多西环素主要有关物质的抗菌活性由强至弱顺序为美他环素、4-表多西环素（杂质C）、β-多西环素、2-乙酰-2脱氨甲酰多西环素（杂质F）；细胞毒性由大至小的顺序为杂质F、β-多西环素、杂质C、美他环素；致斑马鱼胚胎死亡和发育畸形由强至弱的顺序为杂质C、美他环素、杂质F、β-多西环素。结论：盐酸多西环素中毒性较强且抗菌作用较弱的杂质C及杂质F应单独的控制。

Objective: To compare the in vitro antibacterial activity and toxicity of doxycycline hydrochloride with that of its main related substance,and to provide the reference basis for developing the limit of related substance in doxycycline.Methods: The in vitro antibacterial activity was evaluated by the disc diffusion test and broth macro dilution antifungal susceptibility test.The toxicity of doxycycline's substances was evaluated by Chinese hamper lung cell and zebrafish embryo model.Results: The order of main substances' antibacterial activity from the strong to the weak was from metacycline,4-epidoxycycline(impurity C),β-epidoxycycline,to acetyl-2-decarbamoyldoxycycline (impurity F).The related impurities' cytotoxicity was in the order of impurity F,β-epidoxycycline,impurity C,metacycline.The lethal and developmental toxicity order of main substances was from impurity C,metacycline,impurity F,β-epidoxycycline.Conclusion: The related impurities of impurity C and impurity F in doxycycline hydrochloride showed strong toxicity and weak antibacterial,so they should be individually controlled.