Green Stability Indicating Organic Solvent-Free HPLC Determination of Remdesivir in Substances and Pharmaceutical Dosage Forms

Abstract

A green liquid chromatographic method is considered in this work to minimize the environmental impact of waste solvents. One important principle is to replace or eliminate the use of hazardous organic solvents. Organic impurities in any active pharmaceutical ingredient could arise either during the process of its synthesis, or as degradation products developed throughout the shelf-life. Remdesivir (RDS) is an antiviral drug, approved by the US Food and Drug Adminstration (-FDA), to treat SARS-Cov-2 virus during its pandemic crisis. We studied the stability of remdesivir against several degradation pathways using the organic solvent-free liquid chromatographic technique. Separation was performed on RP-C18 stationary phase using mixed-micellar mobile phase composed of a mixture of 0.025 M Brij-35, 0.1 M sodium lauryl sulfate (SLS), and 0.02 M disodium hydrogen phosphate, adjusted to pH 6.0. The mobile phase flow rate was 1 mL min−1, and detection was carried out at a wavelength of 244 nm. We profiled the impurities that originated in mild to drastic degradation conditions. The method was then validated according to International Conference of Harmonization (ICH) guidelines within a linearity range of 5–100 μg mL−1 and applied successfully for the determination of the drug in its marketed dosage form. A brief comparison was established with reported chromatographic methods, including a greenness assessment on two new metrics (GAPI and AGREE). This study is the first to be reported as eco-friendly, solvent-free, and stability indicating LC methodology for RDS determination and impurity profiling.

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

“…For comparison of the proposed method with previously published stability indicating HPLC methods ( Ibrahim et al, 2021 ; Hamdy et al, 2021 ; Ramakrishna Reddy et al, 2021 ; Surabhi and Jaina, 2021 ), we first applied the GAPI tool to attain an inclusive greenness evaluation and rational ranking of the methods. This metric offers a thorough ecological evaluation of the whole method starting from sample preparation step up to the final determination step.…”

“…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 ).…”

Two Green Micellar HPLC and Mathematically Assisted UV Spectroscopic Methods for the Simultaneous Determination of Molnupiravir and Favipiravir as a Novel Combined COVID-19 Antiviral Regimen

“…The mRNA vaccine, BNT162b2, which was developed by Pfizer was reported to be uptaken into human liver cells and incorporated within the host DNA [ 5 ]. On the other hand, the development and approval process of new drug molecule is strict and requires a long time to establish its safety profile before human consumption [ 6 ]. Therefore, scientists focused their trials on repurposing previously approved antiviral agents for postinfection treatments.…”