DEVELOPMENT AND VALIDATION OF RESIDUAL SOLVENT DETERMINATION BY GAS CHROMATOGRAPHY- FID IN EDARAVONE FORMULATION

An accurate, precise, robust, and sensitive gas chromatographic method with flame ionization detection (GC-FID) was developed for the determination of residual solvents in edaravone injection formulation. Impurities may be present in final pharmaceutical products. However, their presence and control in drug substances and drug products are regulated according to pharmacopoeial standards and ICH guidelines. Pharmaceutical products generally contain three types of impurities: organic, inorganic, and residual solvents. Residual solvents are volatile organic chemicals used during the manufacture of drug substances or products. In this study, a simple and sensitive GC method was developed and validated for the determination of methanol as a residual solvent in edaravone formulation. Chromatographic separation was performed on an AB-Innowax polar capillary column (30 m × 0.25 mm × 0.25 µm) using nitrogen as carrier gas at a flow rate of 1.7 mL/min. The temperature program was set at 50 ºC (1 min), increased to 70 ºC (2 min), then raised to 200 ºC at 10 ºC/min then raised to 250 ºC and held for 5 min. Injection was performed in split mode (7:1) with 1 µL volume. Methanol retention time was 2.482 min. Injector and detector temperatures were 250 ºC. DMSO was used as solvent. The method showed linearity (0.6–3.0 µg/mL; r² = 0.9994) and was validated as per ICH Q2(R2) guidelines. Successful application confirmed suitability for methanol determination in edaravone injection because the only one solvent methanol was used during the synthesis of edaravone (HY-B0099).