RP-HPLC Method Development, Validation, and Drug Repurposing of Sofosbuvir Pharmaceutical Dosage Form: A Multidimensional Study

• Published in: Environmental research 2022-09, Vol.212 (Pt C), p.113282-113282, Article 113282
• Main Authors: Mangrio, Ghulam Rasool, Maneengam, Apichit, Khalid, Zunera, Jafar, Tassadaq Hussain, Chanihoon, Ghulam Qadir, Nassani, Rayan, Unar, Ahsanullah
• Format: Article
• Language: English
• Subjects: Chemicals; Coronavirus disease 2019; Drug repurposing; Environmental epidemiology; HPLC; In-silico studies; Sofosbuvir; Toxicology
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2022.113282

A smooth, exceptionally sensitive, correct, and extra reproducible RP-HPLC technique was developed and demonstrated to estimate Sofosbuvir (SOF) in pharmaceutical dosage formulations. This process was carried out by Agilent High-Pressure Liquid Chromatograph 1260 with GI311C Quat. Pump, Phenomenex Luna C-18 (150 mm × 4.6 mm × 5 μm) (USA), and Photodiode Array Detector (PDA) G1315D. The cell section, including acetonitrile and methanol with 80:20 v/v and solution (B) 0.1% phosphoric acid (40:60), was used for the study. However, 10 μL of the sample was injected with a drift flow of 1 mL/min. The separation occurred at a column temperature of 30 °C, and the eluents used PDA set at 260 nm. The retention time of SOF was 5 min. The calibration curve was modified linearly within the range of 0.05–0.15 mg/mL with a correlation coefficient of 0.99 and genuine linear dating among top vicinity and consciousness in the calibration curve. The detection and quantification restrictions were 0.001 and 0.003 mg/mL, respectively. SOF recovery from pharmaceutical components ranged from 98% to 99%. The percentage assay of SOF was 99%. Analytical validation parameters, such as specificity, linearity, precision, accuracy, and selectivity, were studied, and the percentage relative standard deviation (%RSD) was less than 2%. All other key parameters were observed within the desired thresholds. Hence, the proposed RP-HPLC technique was proven effective for developing SOF in bulk and pharmaceutical pill dosage forms. SOF was found to interact with SARS-COV-2 nsp12, and molecular docking results revealed its high affinity and firm binding within the active site groove of nsp12. The key interacting residues include; LYS-72, GLN-75, MET-80 ALA-99, ASN-99, TRP-100, TYR-101 with ASN-99 and TRP-100 forming hydrogen bonds. Molecular Dynamics simulation of SOF and nsp12 complex elucidated that the system was stable throughout 20ns. Therefore, this drug repurposing strategy for SOF can be used for treating COVID-19 infections by performing animal experiments and accurate clinical trials in the future. •The method proposed for this analysis has been alidated according to WHO, Health Canada and ICH Q2 (R1) procedures.•To develop a precise, rapid, accurate and sensitive RP- HPLC method to analyze SOF in pharmaceutical dosage and bulk drug forms.•The drug repurposing of SOF elucidated its role in inhibiting other viral infections inlcuding SARS-CoV-2.•Molecular Docking of SOF with SARS-COV-2 n