Identification, isolation and characterization of potential degradation product in risperidone tablets

J Pharm Biomed Anal. 2008 Jan 7;46(1):165-9. doi: 10.1016/j.jpba.2007.08.008. Epub 2007 Aug 14.

Abstract

One unknown impurity (degradation product) present at a level below 0.1% in the initial samples increased to a level of 0.5% in 6M/40 degrees C/75% RH stability samples of risperidone tablets was detected by gradient reverse-phase high-performance liquid chromatography (HPLC). This impurity was isolated using reverse-phase preparative liquid chromatography. Based on the spectral data the structure of this impurity is characterized as 3-[2-[4-[6-fluoro-1,3-benzoxazol-2-yl]piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a] pyrimidin-4-one. Structural elucidation of this impurity by spectral data ((1)H NMR, (13)C NMR, DEPT, MS and IR), formation and mechanism has been discussed in detail.

MeSH terms

  • Antipsychotic Agents / chemistry
  • Chromatography, High Pressure Liquid / methods
  • Drug Contamination*
  • Drug Stability
  • Hot Temperature
  • Isoxazoles / chemistry*
  • Isoxazoles / isolation & purification
  • Light
  • Magnetic Resonance Spectroscopy / methods
  • Mass Spectrometry / methods
  • Models, Chemical
  • Molecular Structure
  • Risperidone / analogs & derivatives*
  • Risperidone / chemistry*
  • Risperidone / isolation & purification
  • Tablets

Substances

  • 3-(2-(4-(6-fluoro-1,3-benzoxazol-2-yl)piperidin-1-yl)ethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido(1,2-a)pyrimidin-4-one
  • Antipsychotic Agents
  • Isoxazoles
  • Tablets
  • Risperidone