Identification and Characterization of Potential Impurities of Dronedarone Hydrochloride

Six potential process related impurities were detected during the impurity profile study of an antiarrhythmic drug substance, Dronedarone (<b>1</b>). Simple high performance liquid chromatography and liquid chromatography–mass spectrometry methods were used for the detection of these process impurities. Based on the synthesis and spectral data (MS, IR, ¹H NMR, ¹³C NMR, and DEPT), the structures of these impurities were characterized as 5-amino-3-[4-(3-di-<i>n</i>-butylaminopropoxy)­benzoyl]-2-<i>n</i>-butylbenzofuran (impurity I); <i>N</i>-(2-butyl-3-(4-(3-(dibutylamino)­propoxy)­benzoyl)­benzofuran-5-yl)-<i>N</i>-(methylsulfonyl)­methanesulfonamide (impurity II); <i>N</i>-(2-butyl-3-(4-(3-(dibutylamino)­propoxy)­benzoyl)­benzofuran-5-yl)-1-chloromethanesulfonamide (impurity III); <i>N</i>-{2-propyl-3-[4-(3-dibutylaminopropoxy)­benzoyl]­benzofuran-5-yl}­methanesulfonamide (impurity IV); <i>N</i>-(2-butyl-3-(4-(3-(dibutylamino)­propoxy)­benzoyl)­benzofuran-5-yl)­formamide (impurity V); and (2-butyl-5-((3-(dibutylamino)­propyl)­amino)­benzofuran-3-yl)­(4-(3-(dibutylamino)­propoxy)­phenyl)­methanone (impurity VI). The synthesis and characterization of these impurities are discussed in detail