title: Identification, isolation and characterization of potential process-related impurity and its degradation product in vildagliptin.
abstract: Vildagliptin is a member of a new class of oral anti-diabetic drug. One unknown impurity was identified in the range of 0.01-0.06% in different laboratory batches of vildagliptin along with known impurities by HPLC analysis. The structure of unknown impurity was proposed as (2S)-1-[2-[(3-hydroxyadamantan-1-yl)imino]acetyl]pyrrolidine-2-carbonitrile (Impurity-E) using LC/ESI-MS(n) study. The unknown impurity was found to be unstable in diluent (H2O:CH3CN) and degrading into another stable impurity. The degraded stable impurity was isolated from enriched reaction crude sample by semi preparative liquid chromatography. The structure of stable impurity was established using FT-IR, NMR ((1)H, (13)C and DEPT), 2D NMR (HSQC, HMBC and COSY) and mass spectral data as (8aS)-3-hydroxy-octahydropyrrolo[1,2-a]piperazine-1,4-dione (Impurity-F). Impurity identification, abnormal behaviour of impurity-E, isolation of impurity-F, fragmentation mechanism and structural elucidation were also discussed.
authors.affiliation: Micro Labs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigini Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Micro Labs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigini Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India.
authors.forename: Subba Rao
authors.initials: SR
authors.lastname: Devineni
authors.affiliation: Micro Labs Ltd., Analytical Research Department, API R&D Centre, Bommasandra-Jigini Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India.
authors.forename: Gurmeet
authors.initials: G
authors.lastname: Singh
authors.affiliation: Micro Labs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigini Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India.
authors.forename: A
authors.initials: A
authors.lastname: Kadirappa
authors.affiliation: Micro Labs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigini Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India.
authors.forename: Shailendra Kumar
authors.initials: SK
authors.lastname: Dubey
authors.affiliation: Micro Labs Ltd., Chemical Research Department, API R&D Centre, Bommasandra-Jigini Link Road, KIADB INDL Area, Bommasandra, Bangalore 560105, Karnataka, India. Electronic address: pramodkumar@microlabs.in.
authors.forename: Pramod
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000032:analysis / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000032:analysis*; D004340:Drug Contamination / Q000517:prevention & control*; D015394:Molecular Structure; D009570:Nitriles / Q000032:analysis*; D011759:Pyrrolidines / Q000032:analysis* / Q000302:isolation & purification*; D021241:Spectrometry, Mass, Electrospray Ionization; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D000077597:Vildagliptin
chemical_list: C000611380:1-(2-((3-hydroxyadamantan-1-yl)imino)acetyl)pyrrolidine-2-carbonitrile; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane
keywords: Identification; Impurity degradation; Isolation; LC/ESI–MS(n); NMR; Vildagliptin