Application of Liquid Chromatography Tandem Mass Spectrometry for Trace‐Level Detection of Potential Genotoxic Impurities in Edaravone Bulk and Parenteral Dosage Forms

Edaravone (EVN) is a potent free radical scavenger that has garnered considerable interest in the medical domain for its therapeutic efficacy. The drug is employed in the management of various neurological conditions, particularly amyotrophic lateral sclerosis and ischemic stroke. Notwithstanding its recognized therapeutic benefits, the presence of genotoxic impurities in EVN poses possible risks that necessitate thorough evaluation and regulation. The categorization of impurities requires the determination of acceptable intake thresholds in accordance with regulatory standards, especially concerning human consumption, which is the focus of this study. The investigation suggests the likely development of two impurities, namely phenylhydrazine (PHE) and Aniline (ANL). Also, the analysis confirms that both impurities are highly potent and classed as 1, with a permissible level of 25.0 ppm. A quantification method utilizing liquid chromatography tandem mass spectrometry has been developed and validated in compliance with regulatory standards. The technique employs formic acid, methanol, and acetonitrile as constituents of the mobile phase, executed in a gradient program at a flow rate of 0.8 mL/min. The separation employed a C18 column of 150 × 4.6 mm with a particle size of 5 µm. A multiple reaction monitoring mass measurement method was utilized for the precursor/product m/z ions of 109.0/92.0 for PHE and 93.7/77.1 for ANL.