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

Keywords:

• characterization
• citalopram
• impurity
• LC-MS/MS
• NMR
• semi-preparative HPLC

ACKNOWLEDGMENT

The authors are thankful to the management of Jubilant Life Sciences Limited for providing necessary facilities. The authors would like to thank Dr. Subhash Chandra Joshi, Mr. Mohan Kumar, Mr. I. Sridhar, Mr. Amber Bharti, and Mr. Saroj Kumar Paul for their co-operation in carrying out this work. We would also like to thank Dr. Dharam Vir for continuous encouragement throughout the course of this article.

Notes

s = singlet, d = doublet, t = triplet, m = multiplet, numbering has been done NMR characterization.