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Stress degradation of edaravone: Separation, isolation and characterization of major degradation products
Author(s) -
Baghel Madhuri,
Rajput Sadhana J.
Publication year - 2018
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4146
Subject(s) - degradation (telecommunications) , chemistry , edaravone , phenylhydrazine , chromatography , forced degradation , organic chemistry , high performance liquid chromatography , reversed phase chromatography , pharmacology , medicine , telecommunications , computer science
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 C 18 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.