Document Type : Full research article
Department of Pharmaceutical Quality Assurance, PES’s Modern college of Pharmacy, Nigdi, Pune Maharashtra, India
Department of Pharmaceutical Chemistry, PES’s Modern college of Pharmacy, Nigdi, Pune Maharashtra, India
The purpose of this study was to create, optimise, and validate a high-performance thin layer chromatographic (HPTLC) method for identifying Molnupiravir (MOL) and its impurity (IMP-MOL). (3aR,4R,6R,6aR) -6-(4-(hydroxyamino) -2-oxopyrimidin-1(2H)-yl) Molnupiravir A is 2,2 dimethyltetrahydrofuro [3,4-d][1,3]dioxol-4-yl)methyl isobutyrate (MOL IMP) Over concentration ranges of 0.1 µg/band to 0.6 µg/band and 0.02 to 0.6 µg/band, the proposed technique was employed to analyse Molnupiravir and its impurity, with mean percentage recovery of 99.92% ±1.521 and 99.28% ±2.296, respectively. This method has been done with the separation of two components and ends with the densitometric measurement of the separated peaks at 276 nm. The separation was done on silica gel HPTLC F254 plates with a Toluene: n-Butanol: Methanol: Water developing system (5:3:1.5:0.5, by volume). The MOL was kept under conditions like oxidative, hydrolytic, thermal stress, and photolytic tests that the International Conference on Harmonization (ICH) requires. In acid, alkali, and oxidative hydrolysis, the MOL was unstable, but it was not affected by acidic, heat or UV light. The alkaline degradation of Molnupiravir was studied using the proposed HPTLC approach. The degradant are separated using HPTLC method, and their structures are confirmed using IR, MS, and NMR spectrum data.
- WHO coronavirus (COVID-19) dashboard; Geneva: World Health Organization, 2021 (https://covid19.who.int).
- Stokes, E.K., Zambrano, L.D., Anderson, K.N., et al.; Coronavirus disease 2019 case surveillance — United States, January 22– May 30, 2020; MMWR Morb Mortal Wkly Rep 2020;69:759-65.
- Ko, J.Y., Danielson, M.L., Town, M., et al.; Risk factors for coronavirus disease 2019 (COVID-19)–associated hospitalization: COVID-19–associated hospitalization surveillance network and behavioral risk factor surveillance system; Clin Infect Dis 2021;72(11):e695-e703.
- Kompaniyets, L., Goodman, A.B., Belay, B., et al.; Body mass index and risk for COVID-19-related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death — United States, March–December 2020; MMWR Morb Mortal Wkly Rep 2021;70:355-61
- Yoon, J.J., Toots, M., Lee, S., et al.; Orally efficacious broad-spectrum ribonucleoside analog inhibitor of influenza and respiratory syncytial viruses; Antimicrob Agents Chemother 2018;62(8):e00766-18.
- Cox, R.M., Wolf, J.D., Plemper, R.K.; Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets; Nat Microbiol 2021;6:11-8.
- Sheahan, T.P., Sims, A.C., Zhou, S., et al.; An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice; Sci Transl Med 2020;12(541):eabb5883.
- Wahl, A., Gralinski, L.E., Johnson, C.E., et al.; SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801; Nature 2021;591:451-7.
- Abdelnabi, R., Foo, C.S., De-Jonghe, S., Maes, P., Weynand, B., Neyts, J.; Molnupiravir inhibits the replication of the emerging SARS-CoV-2 variants of concern (VoCs) in a hamster infection model; J Infect Dis 2021;224:749-53.
- Agostini, M.L., Pruijssers, A.J., Chappell, J.D., et al.; Small-molecule antiviral betad-N4 -hydroxycytidine inhibits a proofreading-intact coronavirus with a high genetic barrier to resistance; J Virol 2019; 93(24):e01348-19.
- Urakova, N., Kuznetsova, V., Crossman, D.K., et al.; β-d-N4 -hydroxycytidine is a potent anti-alphavirus compound that induces a high level of mutations in the viral genome; J Virol 2018;92(3):e01965-e17.
- Grobler, J., Strizki, J., Murgolo, N., et al.; Molnupiravir maintains antiviral activity against SARS-CoV-2 variants in vitro and in early clinical studies. In: Proceedings and abstracts of IDWeek 2021, September 29–October 3, 2021; Arlington, VA: Infectious Diseases Society of America, 2021
- Painter, G.R., Bowen, R.A., Bluemling, G.R., DeBergh, J., Edpuganti, V., Gruddanti, P.R., Guthrie, D.B., Hager, M., Kuiper, D.L., Lockwood, M.A., Mitchell, D.G., Natchus, M.G., Sticher, Z.M., Kolykhalov, A.A.; The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal Venezuelan equine encephalitis virus infection. 2019; Antiviral Res 171:104597; https://doi.org/10.1016/j.antiviral.2019.104597.
- ICH Guideline Q3A (R); Impurities in New Drug Substances; February 7, 2002.
- ICH Guideline Q1A (R2); Stability Testing of New Drug Substances and Product; February, 2003.