title: Identification, isolation and characterization of potential degradation products in pioglitazone hydrochloride drug substance.
abstract: During stress degradation studies of pioglitazone hydrochloride, one major unknown oxidative degradation impurity and two major unknown base degradation impurities were identified by LC-MS. These impurities were isolated using preparative liquid chromatography. Based on the spectral data (1H NMR, 13C NMR, MS and IR), oxidative degradation impurity, base degradation impurity-1 and base degradation impurity-2 were characterized as pioglitazone N-oxide, 3-(4-(2-(5-ethylpyridine-2yl) ethoxy) phenyl)-2-mercaptopropanoic acid and 2-(1-carboxy-2-{4-[2-(5-ethylpyridine-2yl)-ethoxy] phenyl}-ethyl disulfanyl)-3-{4-[2-(5-ethylpyridine-2yl)-ethoxy] phenyl propanoicacid, respectively. The formation and mechanism of these impurities were discussed and presented.
authors.affiliation: Analytical Research, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Visakhapatnam, India.
authors.forename: K
authors.initials: K
authors.lastname: Ramulu
authors.forename: T Thilak
authors.initials: TT
authors.lastname: Kumar
authors.forename: S Radha
authors.initials: SR
authors.lastname: Krishna
authors.forename: R
authors.initials: R
authors.lastname: Vasudev
authors.forename: M
authors.initials: M
authors.lastname: Kaviraj
authors.forename: B M
authors.initials: BM
authors.lastname: Rao
authors.forename: N Someswara
authors.initials: NS
authors.lastname: Rao
mesh_terms: D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives* / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D007004:Hypoglycemic Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D000077205:Pioglitazone; D011422:Propionates / Q000032:analysis*; D011725:Pyridines / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D045162:Thiazolidinediones / Q000737:chemistry*
chemical_list: C549290:2-(1-carboxy-2-(4-(2-(5-ethylpyridine-2yl)-ethoxy) phenyl)-ethyl disulfanyl)-3-(4-(2-(5-ethylpyridine-2yl)-ethoxy)) phenyl propanoic acid; C549288:3-(4-(2-(5-ethylpyridine-2yl) ethoxy) phenyl)-2-mercaptopropanoic acid; D007004:Hypoglycemic Agents; D011422:Propionates; D011725:Pyridines; D045162:Thiazolidinediones; D015097:3-Mercaptopropionic Acid; D000077205:Pioglitazone