Structural elucidation of process-related impurities in escitalopram by LC/ESI-MS and NMR

Three impurities were detected in escitalopram bulk drug by HPLC-UV and LC/MS. These impurities were marked as ESC-I, -II and -III. Two of these impurities (ESC-II and -III) were unknown and have not been reported previously. Ion trap and Q-TOF mass analyzer were employed to carry out MS/MS and accurate mass analysis of these unknown impurities. Based on mass spectrometric data and synthetic specifics the structures of ESC-II and -III were proposed as N-(chloromethyl)-3-[5-cyano-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-1-yl]-N,N-dimethylpropan-1-aminium and N-(chloromethyl)-4-[4-cyano-2-(hydroxymethyl)phenyl]-4-(4-fluorophenyl)-4-hydroxy-N,N-dimethylbutan-1-aminium respectively. The impurities were isolated by semi-preparative HPLC and structures were confirmed by NMR spectroscopy. The plausible mechanism for the formation of impurities is also discussed.