Stress Degradation of Edaravone: Separation, Isolation and Characterization of Major Degradation Products

Biomed Chromatogr. 2018 Apr;32(4). doi: 10.1002/bmc.4146. Epub 2017 Dec 21.

Abstract

In the present study the International Conference on Harmonization-prescribed stress degradation was carried out to study the degradation profile of edaravone. To establish a Quality by Design (QbD)-assisted stability-indicating assay, the reaction solutions in which different degradation products were formed were mixed. Plackett Burman and central composite design were used to screen and optimize experimental variables to resolve edaravone and its impurities with good peak symmetry using an RP C18 column. The method was validated according to International Conference on Harmonization guidelines. Seven unknown and two known degradation products were identified and characterized by LC-MS/MS. Two major degradation products formed under thermal degradation were isolated and characterized as 4-(4,5-dihydro-3-methyl-5-oxo-1-phenyl-1H-pyrazol-4-yl-4-(4,5-dihydro-5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and 3-hydroxy-dihydro-thiazolo[1-(2-methyl-buta-1,3dienyl)-1-phenylhydrazine]5-one. The degradation pathways of degradants were proposed based on m/z values.

Keywords: ALS; LC-MS/MS; QbD; edaravone; radicut.

MeSH terms

  • Antipyrine / analogs & derivatives*
  • Antipyrine / analysis
  • Antipyrine / chemistry
  • Antipyrine / isolation & purification
  • Chromatography, Liquid / methods
  • Drug Contamination
  • Drug Stability
  • Edaravone
  • Limit of Detection
  • Linear Models
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods
  • Temperature

Substances

  • Edaravone
  • Antipyrine