title: Structural elucidation of a process-related impurity in ezetimibe by LC/MS/MS and NMR.
abstract: A major process-related impurity associated with the synthesis of ezetimibe was detected by LC-MS. The isolated impurity was found not to have been previously reported. Based on LC/MS/MS studies and accurate mass data, the structure of that impurity was proposed to be 2-(4-hydroxybenzyl)-N,5-bis-(4-fluorophenyl)-5-hydroxypentanamide. The postulated structure was unambiguously confirmed with the help of the NMR and IR analyses of a synthetically obtained sample. The chemical shift of the labile proton of that new entity was assigned by a 2D-NOESY NMR experiment. A rationalization for the formation of this impurity is provided.
authors.affiliation: Department of Chemistry, K.J. Somaiya College of Science and Commerce, Vidyavihar (E), Mumbai 400077, India. drbhanuraman@rediffmail.com
authors.forename: Bhanu
authors.initials: B
authors.lastname: Raman
authors.forename: Brajesh A
authors.initials: BA
authors.lastname: Sharma
authors.forename: Rahul
authors.initials: R
authors.lastname: Butala
authors.forename: Pradeep D
authors.initials: PD
authors.lastname: Ghugare
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D001384:Azetidines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D004340:Drug Contamination; D000069438:Ezetimibe; D000960:Hypolipidemic Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017550:Spectroscopy, Fourier Transform Infrared; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D001384:Azetidines; D000960:Hypolipidemic Agents; D000069438:Ezetimibe