Green adherent degradation kinetics study of Nirmatrelvir, an oral anti-COVID-19: characterization of degradation products using LC–MS with insilico toxicity profile

Abstract

AbstractThe SARS-CoV-2 virus sets up a global catastrophe, and countries all around the world made significant efforts to halt the spread. Nirmatrelvir (NMV) was lately approved by the FDA as a safe and well-tolerated oral direct-acting antiviral medication for SARS-CoV-2 virus infection. Therefore, a fast completely validated stability indicating method was established-for the first time- for NMV determination. The study used NaOH, HCl, neutral, H2O2, and sunlight to test NMV stability under various stress conditions followed by kinetics degradation investigation and derivation of Arrhenius plot. The analysis was performed using Agilent Zorbax Eclipse-C18 column (5 µm, 4.6 × 250 mm) with a mobile phase consisting of acetonitrile: 50 mM ammonium acetate, pH = 5 (50:50, v/v, respectively) at a flow rate of 1.0 mL/min with 5 min run time. Diode array detector (DAD) was set at 225 nm to quantify NMV at the concentration range of 5–500 µg/mL with LOD and LOQ of 0.6 and 2 µg/mL, respectively. Method’s greenness was assessed using different metrics including Analytical Eco-Scale, Greenness Assessment Procedure Index, GAPI, and Analytical Greenness, AGREE. A thorough study of stress stability revealed that NMV was more susceptible to alkaline hydrolysis compared with acid hydrolysis. In contrast, it was found that NMV remained stable when subjected to oxidative, neutral, and sun-induced degradation conditions. Moreover, acid and alkali-induced hydrolysis were found to follow pseudo first order kinetics. Consequently, the half lifetime of the studied degradation conditions at room temperature were calculated using the Arrhenius plot. The mechanism of the degradation pathways under stress circumstances was proposed using LC–MS-UV. Toxicities of the proposed degradation products were assessed using ProTox-II, along with the parent medication NMV, and were shown to be hardly hazardous.