title: Investigation and structural elucidation of a process related impurity in candesartan cilexetil by LC/ESI-ITMS and NMR.
abstract: Four impurities were detected in candesartan cilexetil bulk drug samples by HPLC and LC/MS. These impurities were marked as CDC-I, II, III and IV. One of the impurities CDC-II was unknown and has not been reported previously. An optimized method using liquid chromatography coupled with electrospray ionization ion trap mass spectrometry (LC/ESI-ITMS) in positive ion mode has been developed to carry out structural identification of unknown impurity. Based on mass spectrometric data and synthetic specifics the structure of CDC-II was proposed as 2-ethoxy-1-[[2'-(1-ethyl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid ethyl ester. The impurity was isolated by semi-preparative HPLC and structure was confirmed by NMR spectroscopy. The plausible mechanism for the formation of impurities is also discussed.
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: Ganesh
authors.initials: G
authors.lastname: Mahale
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Singh
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000032:analysis* / Q000138:chemical synthesis; D001562:Benzimidazoles / Q000032:analysis* / Q000138:chemical synthesis; D001713:Biphenyl Compounds / Q000032:analysis* / Q000138:chemical synthesis; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D004339:Drug Compounding; D004340:Drug Contamination; D004951:Esterification; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011786:Quality Control; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods*; D013777:Tetrazoles / Q000032:analysis* / Q000138:chemical synthesis
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C077793:candesartan cilexetil