Identification and characterization of potential impurities of rabeprazole sodium

J Pharm Biomed Anal. 2007 Mar 12;43(4):1262-9. doi: 10.1016/j.jpba.2006.10.017. Epub 2006 Nov 28.

Abstract

Six impurities in rabeprazole sodium bulk drug substance were detected by a simple isocratic high performance chromatographic method (HPLC) whose area percentage ranged from 0.60 to 1.46%. LC-MS was performed to identify the mass of the impurities. A thorough study was undertaken to characterize these impurities. These impurities were synthesized, subsequently characterized and were co-injected with the sample containing impurities and are found to be matching with the impurities in the sample. Based on their spectral data (IR, NMR and MS), these impurities were characterized as 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl] methyl]thio]-1H-benzimidazole (impurity I); 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl] methyl] sulfonyl]-1H-benzimidazole (impurity II); 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl-1-oxide] methyl] sulfonyl]-1H-benzimidazole (impurity III); 2-[[[4-(3-methoxypropoxy)-3-methyl] pyridin-2-yl]methanesulfinyl]-1-[[4-(3-methoxypropoxy)-3-methyl]pyridin-2-ylmethyl]-1H-benzimidazole (impurity IV); 2-[[[4-methoxy-3-methyl-2-pyridinyl] methyl] sulfinyl]-1H-benzimidazole (impurity V); 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridine-1-oxide] methyl] sulfinyl]-1H-benzimidazole (impurity VI).

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / analysis*
  • 2-Pyridinylmethylsulfinylbenzimidazoles / chemistry
  • Anti-Ulcer Agents / analysis*
  • Anti-Ulcer Agents / chemistry
  • Chromatography, High Pressure Liquid
  • Drug Contamination
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Rabeprazole
  • Spectroscopy, Fourier Transform Infrared

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Anti-Ulcer Agents
  • Rabeprazole