Accelerated stability study of the ester prodrug remdesivir: Recently FDA‐approved Covid‐19 antiviral using reversed‐phase‐HPLC with fluorimetric and diode array detection

Abstract

Remdesivir (RDV) is the first antiviral drug, approved by the Food and Drug Administration, to treat severe acute respiratory syndrome coronavirus 2. RDV is a relatively new chemical entity, 'ester prodrug', with no reported stability profile.Due to the urgency of its use and thus fast production, it is important to develop a stability-indicating method for its assay. Chromatographic separation was carried out on a C18 column (250 Â 4.6 mm, 5 μm) with dual detection: diode array at 240 nm and fluorescence at λ ex/em 245/390 nm. Isocratic elution of acetonitrile and distilled water (acidified with phosphoric acid, pH 4) in the ratio of 55:45 (v/v), respectively, was used. The linearity range using HPLC-diode array detection was 0.1-15 μg/mL, whereas that using fluorimetric detection was 0.05-15 μg/mL. As per the International Conference on Harmonization guidelines, RDV has been degraded by accelerated alkaline, acidic, neutral hydrolysis, oxidative, heat, and photolytic stress conditions. Possible degradation hypothesis of the parent molecule has been suggested and illustrated. The 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. The developed methods were fully validated and proved suitable for quality control routine analysis of RDV in raw material and pharmaceutical dosage forms.

Eco-friendly stability-indicating HPTLC micro-determination of the first FDA approved SARS-CoV-2 antiviral prodrug Remdesivir: Study of degradation kinetics and structural elucidation of the degradants using HPTLC-MS

“…It is worthy to mention that the degradation hypothesis presented in schemes (1 & 2) ( Figs. S4 and S5 , supplementary file 1) agrees with a previously reported hypothesis included in a published accelerated stability study of RMD using HPLC-DAD technique ( Hamdy et al, 2021 ).…”

“…Additionally, a reference reversed phase HPLC method ( Hamdy et al, 2021 ) was applied for the determination of RMD in its commercial product. Statistical comparison of the recovery data attained from the proposed method with those obtained from the reference method was performed using the Student's t-test and F-test.…”

“…The current study represents the first ecologically benign, fast and simple stability indicating HPTLC determination of RMD which could be considered as a green, more economic and faster alternative to the previously published stability indicating HPLC procedures ( Ibrahim et al, 2021 ; Hamdy et al, 2021 ; Ramakrishna Reddy et al, 2021 ; Surabhi and Jaina, 2021). Hence, it is more eligible for the routine analysis of RMD in quality control laboratories as well as for testing the drug purity and stability.…”

“…Finally, a comprehensive appraisal of the method's eco-friendliness was carried out using Analytical Eco-scale (AES) ( Gałuszka et al, 2012 ), Green Analytical Procedure Index (GAPI) ( Płotka-Wasylka, 2018 ) and Analytical Greenness (AGREE) ( Pena-Pereira et al, 2020 ) metrics. Besides, a thorough comparison of the method's greenness with other previously published stability indicating HPLC procedures ( Ibrahim et al, 2021 ; Hamdy et al, 2021 ; Ramakrishna Reddy et al, 2021 ; Surabhi and Jaina, 2021 ) and the only reported HPTLC direct determination of RMD ( Noureldeen et al, 2022 ) was also illustrated using the more inclusive GAPI and AGREE metrics.…”

“…Regarding stability indicating assays of RMD, four HPLC methods were reported employing either UV detection ( Ibrahim et al, 2021 ), diode-array detection ( Hamdy et al, 2021 ; Ramakrishna Reddy et al, 2021 ; Surabhi and Jaina, 2021 ) or fluorescence detection ( Hamdy et al, 2021 ). Concerning HPTLC technique, a single recent analytical report was published dealing with the direct determination of RMD and favipiravir in pharmaceutical formulations and human plasma ( Noureldeen et al, 2022 ).…”