替格瑞洛中7个异构体的毒理评价及含量测定研究

目的 研究替格瑞洛中7个异构体的毒理性质，并建立高效液相色谱法对7个异构体的含量进行测定。方法 通过ADMET Predictor软件分析7个异构体的毒理性质，构建7个异构体的统一检验分析方法，并通过该方法对179批次样品的异构体含量进行测定。结果 替格瑞洛片中部分异构体存在肝脏毒性及小鼠致癌的可能性；建立的检验方法可以准确测定各异构体的含量且各异构体间分离度符合要求，179批次样品中7个异构体的含量均符合规定。结论 该系列异构体毒性预测均较小，但其实际效果需具体试验论证，该检验方法能系统地鉴别和测定各异构体的类型和含量，为统一替格瑞洛检验方法提供了重要的参考。

Toxicological assessment and content detection of seven chiral impurities in Ticagrelor Tablets

Objective To completely evaluate the toxic of the seven chiral impurities in Ticagrelor Tablets,and establish a method of high performance liquid chromatography (HPLC) with chiral stationary phase for the detection of the seven chiral impurities. Methods The toxic of the seven chiral impurities in 179 batches of Ticagrelor tablets produced by 8 domestic manufacturers are evaluated by use a toxicity prediction software(ADMET) ,establish a unified method to detect and analyze their content.Results Some of the chiral impurities has a liver toxicity and a carcinogenesis in mice ,but other results indicate no toxicity.The established HPLC method with chiral stationary phase can accurately detect the content of the seven chiral impurities,and the resolution between the chiral impurities meet the requirements. The content of the 7 chiral impurities in 179 batches of Ticagrelor Tablets produced by 8 domestic manufacturers are all meet the prescribed standards.Conclusion The toxic of the seven chiral impurities in ticagrelor tablets appear to be less toxic, but their actual toxic need further exploring. The established HPLC method with chiral stationary phase can systematically identify and detect the types and contents of the seven chiral impurities in Ticagrelor Tablets, which provides an important reference for the unify of standard of Ticagrelor Tablets.