Structural elucidation of a process-related impurity in ezetimibe by LC/MS/MS and NMR.
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.
Raman
Bhanu
B
Department of Chemistry, K.J. Somaiya College of Science and Commerce, Vidyavihar (E), Mumbai 400077, India. drbhanuraman@rediffmail.com
Sharma
Brajesh A
BA
Butala
Rahul
R
Ghugare
Pradeep D
PD
Kumar
Ashok
A
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*
D001384:Azetidines; D000960:Hypolipidemic Agents; D000069438:Ezetimibe