Identification and synthesis of potential impurities of rabeprazole sodium.
Rabeprazole sodium (1, Achiphex) is a gastric proton pump inhibitor. It causes dose-dependent inhibition of acid secretion and is useful as an anti-ulcer agent. In the process for the preparation of 1, two potential unknown impurities were identified in HPLC at levels ranging from 0.05-0.8%. Based on mass spectral data vide LC-MS, the two impurities were characterized as 2-{[(4-chloro-3-methyl-2-pyridinyl) methyl] sulfinyl}-1H-bezimidazole (2, chloro analogue of rabeprazole) and 2-[{(4-methoxy-3-methyl-2-pyridinyl)methyl}sulfinyl]-1H-benzimidazole (3, methoxy analogue of rabeprazole). The structures were unambiguously established by independently synthesizing them and co-injecting in HPLC. To our knowledge, the compounds 2 and 3 have not been reported as process impurities elsewhere.
Pingili
R Reddy
RR
Department of Research and Development, Dr. Reddy's Laboratories Ltd., Bollaram, India.
Jambula
M Reddy
MR
Ganta
M Reddy
MR
Ghanta
M Reddy
MR
Sajja
E
E
Sundaram
V
V
Boluggdu
V Bhaskar
VB
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D064750:Rabeprazole; D013056:Spectrophotometry, Ultraviolet
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D007202:Indicators and Reagents; D064750:Rabeprazole; D009853:Omeprazole