盐酸非索非那定杂质G 的制备及安全性评价  

Preparation and safety evaluation of the fexofenadine hydrochloride impurity G

作　　者：洪芳 周琳 张熠 HONG Fang;ZHOU Lin;ZHANG Yi(Fujian Institute for Food and Drug Quality Control,Fuzhou 350012,China)

机构地区：[1]福建省食品药品质量检验研究院,福建福州350012

出　　处：《中国药物化学杂志》2023年第5期331-338,共8页Chinese Journal of Medicinal Chemistry

摘　　要：目的 制备盐酸非索非那定杂质G,并对其安全性进行评价,为其质量标准研究提供依据。方法 以盐酸非索非那定为起始原料,经酸降解反应得到杂质G,并研究杂质G对小鼠细胞毒性、遗传毒性及生殖毒性的影响。结果与结论盐酸非索非那定杂质G的结构经1H-NMR、13C-NMR、MS、IR、UV谱确证,其收率为57.35%,HPLC法检测纯度为98.23%。杂质G在0.25~2.00 mg·mL^(-1)浓度范围内,随着浓度的增大,细胞毒性也逐渐增大;杂质G在40 mg·kg^(-1)高剂量浓度下对小鼠骨髓细胞染色体无畸变作用,未显示对小鼠骨髓细胞染色体和微核有影响,且无致雄性小鼠生殖毒性作用。制备盐酸非索非那定杂质G的方法简便可行,评价杂质G对小鼠细胞毒性、遗传毒性及生殖毒性的方法真实有效。The fexofenadine hydrochloride impurity G was synthesized,separated and purified using fexofenadine hydrochloride as raw material,and the safety of impurity G was evaluated.The structure of the synthesized impurity G was confirmed by~1H-NMR,~(13)C-NMR,MS,IR,UV and other spectroscopic analysis,and the purity of impurity G was detected by HPLC.The fexofenadine hydrochloride impurity G with 98.23%purity was synthesized and the yield was 57.35%.The effects of impurity G on the cytotoxicity,genetic toxicity and reproductive toxicity of mice were studied.When the concentration of impurity G was in the range of 0.25-2.0 mg·mL^(-1),the cytotoxicity increased gradually with the increase of concentration.At the high dose concentration of 40 mg·kg^(-1),impurity G had no effect on chromosome aberration of mouse bone marrow cells,no effect on chromosome and micronucleus of mouse bone marrow cells,and no reproductive toxicity of male mice.The method of synthesis and separation of impurity G is simple and feasible.The effects of impurity G on cytotoxicity,genetic toxicity and reproductive toxicity in mice were effectively evaluated.This study provides a reference for the study of fexofenadine hydrochloride API related substances,and lays a foundation for the limit control of impurity G.

关 键 词：盐酸非索非那定杂质G 制备 分离纯化 安全性评价 

分 类 号：R914[医药卫生—药物化学]