title: Identification, isolation and characterization of process related impurities in ezetimibe.
abstract: During the synthesis of ezetimibe, two process related impurities were detected were HPLC analysis at levels ranging from 0.05 to 0.8%. These two impurities were isolated by column chromatography and co-injected with ezetimibe sample to confirm the retention times in HPLC. These two impurities were characterized as 2-(4-hydroxybenzyl)-N,5-bis(4-fluorophenyl) pentanamide (impurity-I) and 1-(4-fluorophenyl)-3(3-(4-fluorophenyl)propyl)-4-(4-hydroxyphenyl)azetidin-2-one (impurity-II). Isolation, structural elucidation of these impurities by spectral data ((1)H NMR, (13)C NMR, MS and IR) and probable mechanism of their formation have been discussed.
authors.affiliation: Chemical Research and Development, Aurobindo Pharma Limited, Indrakaran (V), Sangareddy (M), Medak District 502329, Andhra Pradesh, India; Institute of Science and Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 500085, India.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Guntupalli
authors.forename: Uttam Kumar
authors.initials: UK
authors.lastname: Ray
authors.forename: N
authors.initials: N
authors.lastname: Murali
authors.forename: P Badrinadh
authors.initials: PB
authors.lastname: Gupta
authors.forename: Vundavilli Jagadeesh
authors.initials: VJ
authors.lastname: Kumar
authors.forename: D
authors.initials: D
authors.lastname: Satheesh
authors.forename: Aminul
authors.initials: A
authors.lastname: Islam
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000924:Anticholesteremic Agents / Q000032:analysis / Q000737:chemistry*; D001384:Azetidines / Q000032:analysis / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004340:Drug Contamination; D000069438:Ezetimibe; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010756:Phosphoric Acids / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical
chemical_list: D000097:Acetonitriles; D000924:Anticholesteremic Agents; D001384:Azetidines; D010756:Phosphoric Acids; D002784:Cholesterol; C030242:phosphoric acid; D000069438:Ezetimibe; C032159:acetonitrile
keywords: Characterization; Ezetimibe; HPLC; Impurities; Isolation