Identification, isolation and characterization of potential degradation products in pioglitazone hydrochloride drug substance.
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.
Ramulu
K
K
Analytical Research, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Visakhapatnam, India.
Kumar
T Thilak
TT
Krishna
S Radha
SR
Vasudev
R
R
Kaviraj
M
M
Rao
B M
BM
Rao
N Someswara
NS
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*
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