阿伐那非及其有关物质研究进展  

Research Progress of Avanafil and Its Related Substances

作　　者：吴小霞 赵梦梦 刘虎 孙允凯[1,3] WU Xiaoxia;ZHAO Mengmeng;LIU Hu;SUN Yunkai(School of Chemistry and Chemical Engineering,University of South China,Hengyang 421001,China;Harvest Pharmaceutical Co.,Ltd.,Changsha 410220,China;School of Chemical Engineering and Materials,Changzhou Institute of Technology,Changzhou 213032,China)

机构地区：[1]南华大学化学化工学院,湖南衡阳421001 [2]嘉实(湖南)医药科技有限公司,湖南长沙410220 [3]常州工学院化工与材料学院,江苏常州213032

出　　处：《合成化学》2023年第8期651-662,共12页Chinese Journal of Synthetic Chemistry

基　　金：湖南省自然科学基金(2022JJ80096);湖南省教育厅重点项目(20A435)。

摘　　要：阿伐那非作为高选择性的5型磷酸二酯酶抑制剂,是治疗勃起功能障碍的有效药物。阿伐那非易受环境影响,在酸碱性、氧化和光热条件下发生降解产生降解物,在生产工艺过程中存在副反应且产生有机杂质。为了保证药物的安全有效性,必须将有关物质控制在限度范围内,同时建立针对性检测方法以测定阿伐那非含量及鉴定有关物质。本文对阿伐那非的合成工艺进行了概述,同时分析了用于准确检测阿伐那非含量的HPLC法以及基于QbD的HPLC法;液相和其他技术联用的LCMS-IT-TOF、LC-MS/MS和LC-QQQ-MS方法能在测定其含量的同时鉴定物质结构。As a highly selective PDE5 inhibitor,avanafil is an effective drug in the treatment of erectile dysfunction.There are organic impurities in the process of producing avanafil because of side reactions.Avanafil is easily affected by the environment and will degrade under acid,alkaline,oxidation and photothermal conditions.In order to ensure the safety and effectiveness of drugs,related substances must be controlled within the limits.Some specific detection methods were developed to determine the content of avanafil and identify related substances.In this paper,the synthesis process of avanafil is summarized,and the HPLC method and QbD method for the accurate determination of avanafil content are analyzed.LC-MS/MS,LC-QQQ-MS and other methods are used to determine the content and identify the structures of related substances.

关 键 词：勃起功能障碍 阿伐那非 有关物质 高效液相色谱法 液质联用 工艺路线 

分 类 号：O621.3[理学—有机化学]