Accelerated Stability Study of the Ester Prodrug Remdesivir; Recently FDA Approved Covid-19 Antiviral Using RP-HPLC with Fluorimetric and Diode Array Detection.

Hamdy, Mohamed M A; Abdel Moneim, Mona M; Kamal, Miranda F

Remdesivir is the first antiviral drug, approved by the Food and Drug Administration, to treat SARS-CoV-2. Remdesivir is a relatively new chemical entity, "ester prodrug", with no reported stability profile. Due to the urge of its use and thus, fast production, it is important to develop a stability-indicating method for its assay. Chromatographic separation was carried on C18 (250 x 4.6 mm, 5 μm) column with dual detection; Diode-array at 240 nm and fluorescence at λex/em 245/390 nm. Isocratic elution of acetonitrile and distilled water (acidified with phosphoric acid, pH 4) in ratio of 55: 45, v/v respectively was used. HPLC-DAD linearity range was 0.1-15 μg/mL while with fluorimetric detection the range was 0.05-15 μg/mL. As per International Conference on Harmonization guidelines, Remdesivir, has been degraded by accelerated: alkaline, acidic, neutral hydrolysis, oxidative, heat and photolytic stress conditions. Possible degradation hypothesis of the parent molecule was suggested and illustrated. Proposed methods have achieved selective determination of the intact drug with no peaks overlapping in all assumptions. Extensive degradation confirms threatened drug stability at thermal and basic hydrolytic stressing. Developed methods were fully validated and proved suitable for quality control routine analysis of Remdesivir in raw material and pharmaceutical dosage form.