Development and validation of an electroanalytical method for the quantification of antiviral molnupiravir and its application to the pharmaceutical sample

Abstract

In this study, a sensitive, fast, economical, and practical voltammetric method was developed for analysing molnupiravir (MLP), an antiviral drug extensively used during the COVID-19 pandemic, without the need for modifying the glassy carbon (GC) electrode surface. During the electroanalysis, an oxidation peak for MLP was detected at 0.72555 V on the GC electrode. The method exhibited linearity across a concentration range of 1 - 250 µM for MLP with 0.33 µM of detection limit. Furthermore, with a 99.81% recovery from its pharmaceutical form, the method's effectiveness was validated. These results strongly indicate that this method is suitable for routine quality control of molnupiravir and may serve as a model for analysing other antiviral drugs.

Keywords

• Antiviral agent
• molnupiravir
• electroanalytical chemistry
• differential pulse voltammetry

References

1. [1] Qu J-M, Cao B, Chen R-C. Respiratory virus and COVID-19. In: Qu J-M, Cao B, Chen R-C (Eds). COVID-19 The Essentials of Prevention and Treatment. Elsevier, USA, 2021, pp. 1-6. [2] Kotra LP. Viral Disease. In: Enna SJ, Bylund DB (Eds). xPharm: The Comprehensive Pharmacology Reference. Elsevier, New York, 2007, pp. 1-3.
2. [3] Dunn EF, Connor JH. HijAkt: The PI3K/Akt Pathway in Virus Replication and Pathogenesis. In: Shenolikar S.(Ed.) Progress in Molecular Biology and Translational Science. Academic Press, USA, 2012, pp. 223-250. [4] Chappell JD, Dermody TS. Biology of Viruses and Viral Diseases. In: Bennett JE, Dolin R, Blaser MJ (Eds). Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Elsevier/Saunders, Philadelphia, 2015, pp. 1681-1693.e1684.
3. [5] Meganck RM, Baric RS. Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases. Nat Med. 2021; 27(3): 401-410. https://doi.org/10.1038/s41591-021-01282-0.
4. [6] Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395(10229): 1054-1062. https://doi.org/10.1016/S0140-6736(20)30566-3.
5. [7] Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020; 383(27): 2603-2615. https://doi.org/10.1056/NEJMoa2034577.
6. [8] Brown AN, Lang Y, Zhou J, Franco EJ, Hanrahan KC, Bulitta JB, Drusano GL. Why molnupiravir fails in hospitalized patients. Mbio 2022; 13(6): e02916-02922. https://doi.org/10.1128/mbio.02916-22.
7. [9] WHO, World Health Organisation. https://data.who.int/dashboards/covid19/deaths?n=c (accessed 22 August 2024)
8. [10] Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021; 384(5): 403-416. https://doi.org/10.1056/nejmoa2035389.

9. [11] Syed YY. Molnupiravir: First approval. Drugs 2022; 82(4): 455-460. https://doi.org/10.1007/s40265-022-01684-5.
10. [12] Singh AK, Singh A, Singh R, Misra A. Molnupiravir in COVID-19: A systematic review of literature. Diabetes Metab Syndr Clin Res Rev. 2021; 15(6): 102329. https://doi.org/10.1016/j.dsx.2021.102329.
11. [13] Ashour NA, Abo Elmaaty A, Sarhan AA, Elkaeed EB, Moussa AM, Erfan IA, Al-Karmalawy AA. A systematic review of the global intervention for SARS-CoV-2 combating: from drugs repurposing to molnupiravir approval. Drug Des Devel Ther. 2023; 685-715. https://doi.org/10.2147/DDDT.S354841.
12. [14] Mahase E, Covid-19: Molnupiravir reduces risk of hospital admission or death by 50% in patients at risk, MSD reports. https://www.bmj.com/content/375/bmj.n2422 (accessed 22 August 2024)
13. [15] Uslu B, Ozkan SA. Electroanalytical methods for the determination of pharmaceuticals: A review of recent trends and developments. Anal Lett. 2011; 44(16): 2644-2702. https://doi.org/10.1080/00032719.2011.553010.
14. [16] Munoz R, Almeida E, Angnes L. Sample preparation techniques for the electrochemical determination of metals in environmental and food samples. Refer Mod Chem Mol Sci Eng. 2013; 1-10. https://doi.org/10.1016/B978-0-12 409547-2.05750-4. .
15. [17] Yadav SK, Chandra P, Goyal RN, Shim Y-B. A review on determination of steroids in biological samples exploiting nanobio-electroanalytical methods. Anal Chim Acta 2013; 762:14-24. https://doi.org/10.1016/j.aca.2012.11.037.
16. [18] Kulikova T, Porfireva A, Shamagsumova R, Evtugyn G. Voltammetric sensor with replaceable polyaniline‐DNA layer for doxorubicin determination. Electroanalysis 2018; 30(10): 2284-2292. https://doi.org/10.1002/elan.201800331.
17. [19] Liu Y, Wei M, Hu Y, Zhu L, Du J. An electrochemical sensor based on a molecularly imprinted polymer for determination of anticancer drug mitoxantrone. Sens Actuators B Chem. 2018; 255(1): 544-551. https://doi.org/10.1016/j.snb.2017.08.023.
18. [20] Huang D, Wu H, Zhu Y, Su H, Zhang H, Sheng L, Liu Z, Xu H, Song C. Sensitive determination of anticancer drug methotrexate using graphite oxide-nafion modified glassy carbon electrode. Int J Electrochem Sci. 2019; 14(4): 3792 3804. https://doi.org/10.20964/2019.04.03.
19. [21] Karadurmus L, Sahin IF, Kurbanoglu S, Ozkan SA. Electrochemical determination of non-steroidal anti inflammatory drugs. Curr Anal Chem. 2019; 15(4): 485-501. https://doi.org/10.2174/1573411014666180917113920.
20. [22] Karadurmus L, Kır D, Kurbanoglu S, Ozkan SA. Electrochemical analysis of antipsychotics. Curr Pharm Anal. 2019; 15(5): 413-428. https://doi.org/10.2174/1573412914666180710114458.
21. [23] Karadurmus L, Kurbanoglu S, Uslu B, A Ozkan S. Electrochemical DNA biosensors in drug analysis. Curr Pharm Anal. 2017; 13(3): 195-207. https://doi.org/10.2174/1573412912666160422152634.
22. [24] Erk N, Bouali W, Mehmandoust M, Soylak M. An electrochemical sensor for molnupiravir based on a metal organic framework composited with poly (3, 4‐ethylene dioxythiophene): Poly (styrene sulfonate). ChemSelect. 2022; 7(46): e202203325. https://doi.org/10.1002/slct.202203325.
23. [25] Kablan SE, Reçber T, Tezel G, Timur SS, Karabulut C, Karabulut TC, Eroğlu H, Kır S, Nemutlu E. Voltammetric sensor for COVID-19 drug Molnupiravir on modified glassy carbon electrode with electrochemically reduced graphene oxide. J Electroanal Chem. 2022; 920:116579. https://doi.org/10.1016/j.jelechem.2022.116579.
24. [26] Nabil A, Hendawy HA, Abdel-Salam R, Ahmed RM, Shawky A, Emara S, Ibrahim N. A green voltammetric determination of molnupiravir using a disposable screen-printed reduced graphene oxide electrode: Application for pharmaceutical dosage and biological fluid forms. Chemosensors 2023; 11(9): 471. https://doi.org/10.3390/chemosensors11090471.
25. [27] Vural K, Karakaya S, Dilgin DG, Gökçel Hİ, Dilgin Y. Voltammetric determination of Molnupiravir used in treatment of the COVID-19 at magnetite nanoparticle modified carbon paste electrode. Microchem J. 2023; 184: 108195. https://doi.org/10.1016/j.microc.2022.108195.
26. [28] Ozcelikay G, Karadurmus L, Kaya SI, Bakirhan NK, Ozkan SA. A review: New trends in electrode systems for sensitive drug and biomolecule analysis. Crit Rev Anal Chem. 2020; 50(3): 212-225. https://doi.org/10.1080/10408347.2019.1615406.
27. [29] Shahzad S, Karadurmus L, Dogan‐Topal B, Taskin‐Tok T, Shah A, Ozkan SA. Sensitive nucleic acid detection at NH2‐MWCNTs modified glassy carbon electrode and its application for monitoring of gemcitabine‐DNA interaction. Electroanalysis. 2020; 32(5): 912-922. https://doi.org/10.1002/elan.201900597.