CHARACTERIZATION OF AN UNKNOWN IMPURITY IN CITALOPRAM HYDROBROMIDE ACTIVE PHARMACEUTICAL INGREDIENT BY SEMI-PREPARATIVE ISOLATION AND LC-ESI/MSⁿAND NMR

Abstract

& Two impurities were detected during the high-performance liquid chromatographic (HPLC) analysis of citalopram hydrobromide sample by United States Pharmacopoeia (USP) method-I. One of the impurities of the order of 0.25% was found not to be reported previously. Unknown impurity was identified by a liquid chromatography-mass spectrometry (LC-MS) compatible reverse phase isocratic method using electrospray ionization source and ion trap mass analyzer. Impurity was isolated by semi-preparative HPLC followed by characterization using nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (FT-IR), and elemental analysis (EA). Structure of this impurity was unambiguously confirmed by synthesis and the impurity was characterized as 1-[1-(3-Dimethylamino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzo-furan -5-yl]-ethanone. A plausible mechanism for the formation of this impurity is also proposed.