A Validated High-Pressure Liquid Chromatography (HPLC) Method for Molnupiravir

Main Article Content

Gamze Camlik http://orcid.org/0000-0003-3282-8307 Fazli Beyazaslan http://orcid.org/0000-0002-6597-8347 Emre Kara http://orcid.org/0000-0001-8938-8408 Demet Ulker http://orcid.org/0000-0002-4952-3350 Isa Albayrak http://orcid.org/0000-0002-5463-3386 Ismail Tuncer Degim http://orcid.org/0000-0002-9329-4698

Abstract

Molnupiravir is an approved antiviral drug that inhibits RNA replication of viruses. It is approved recently (November 2021) for the treatment of infectious diseases caused by SARS-CoV-2. However, it is reported that Molnupiravir is a nucleoside analogue and shown that nucleoside analogues are reagents that resemble the structure of natural nucleosides. It is widely applied in antiviral and anticancer therapy. Therefore, there is a general need appeared for an efficient, fast, simple, and validated analytical assay method for the quantification of this new product in any samples. We report here that an HPLC method was developed, optimized, and validated for molnupravir. The developed method was found to be easy to apply, cheap, and time-saving. Isocratic elution with 10mM Phosphate Buffer pH:7 / Acetonitrile mixture (80:20) with a Phenomenex C18 column was performed and a photodiode array detector was used for the detection. The total time for the analysis was only 10 minutes. The method was found to be selective, linear, accurate, reproducible, and robust. This proposed method can be easily adapted for molnupravir analyses in pharmaceutical products or in any other biological or non-biological samples.

Keywords: Molnupiravi, Raw material, HPLC, Validation

Article Details

How to Cite
CAMLIK, Gamze et al. A Validated High-Pressure Liquid Chromatography (HPLC) Method for Molnupiravir. Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3127>. Date accessed: 05 nov. 2024. doi: https://doi.org/10.18103/mra.v10i9.3127.
Section
Research Articles

References

[1] Singh AK, Singh A, Singh R, & Misra A. Molnupiravir in COVID-19: A systematic review of literature. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 2021; 15 (6): 102329. https://doi.org/10.1016/j.dsx.2021.102329
[2] Syed YY. Molnupiravir: first approval. Drugs 2022; 1-6. https://doi.org/10.1007/s40265-022-01684-5
[3] Caraco Y, Crofoot GE, Moncada PA, Galustyan AN, Musungaie DB et al. Phase 2/3 trial of molnupiravir for treatment of Covid-19 in nonhospitalized adults. NEJM Evidence 2022; 1(2): EVIDoa2100043. https://doi.org/10.1056/EVIDoa2100043
[4] Jia W, Hu C, Wang Y, Zhang P, Chen HY, Huang S. A Nanopore Based Molnupiravir Sensor, ACS Sens. 2022; 7(5):1564–1571. https://doi.org/10.1021/acssensors.2c00447
[5] Galmarini CM, Mackey JR, Dumontet C. Nucleoside analogues and nucleobases in
cancer treatment, Lancet Oncol. 2002; 3(7): 415–24 https://doi.org/10.1016/s1470-2045(02)00788-x
[6] Değim T, Aka, C, Büyükafşar K, & Cevheroğlu Ş. Simultaneous determination of codeine and ethyl morphine HCl in tablet formulations using LC. Journal of pharmaceutical and biomedical analysis 2001; 26 (1): 15-21. . https://doi.org/10.1016/s0731-7085(01)00392-2
[7] Akay C, Değim İT, Sayal A, Aydin A, Özkan Y et al. Rapid and simultaneous determination of acetylsalicylic acid, paracetamol, and their degradation and toxic impurity products by HPLC in pharmaceutical dosage forms. Turkish Journal of Medical Sciences 2008; 38(2): 167-173.
[8] Guideline, I. H. T. Impurities in new drug substances. Q3A, In International conference of harmonization, 2008.
[9] Guideline, I. H. T. Impurities in new drug products. Q3B (R2), current step, 4, 1-5, 2006.
[10] Liu DQ, Wu L, Sun M, & MacGregor PA. On-line H/D exchange LC–MS strategy for structural elucidation of pharmaceutical impurities. Journal of pharmaceutical and biomedical analysis 2007, 44(2): 320-329. https://doi.org/10.1016/j.jpba.2007.01.019
[11] Reçber T, Timur SS, Kablan SE, Yalçın F, Karabulut TC et al. A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies. Journal of pharmaceutical and biomedical analysis 2022; 214: 114693. https://doi.org/10.1056/EVIDoa2100043
[12] Amara A, Penchala SD, Else L, Hale C, FitzGerald R et al.The development and validation of a novel LC-MS/MS method for the simultaneous quantification of Molnupiravir and its metabolite ß-d-N4-hydroxycytidine in human plasma and saliva. Journal of pharmaceutical and biomedical analysis 2021; 206: 114356. https://doi:10.1016/j.jpba.2021.114356
[13] Uslu B, Özkan SA. Determination of lamivudine and zidovudine in binary mixtures using first derivative spectrophotometric, first derivative of the ratio-spectra and high-performance liquid chromatography–UV methods. Analytica Chimica Acta 2002; 466(1): 175-185. https://doi.org/10.1016/S0003-2670(02)00545-7
[14] Ozkan SA, & Uslu B. Rapid HPLC assay for lamivudine in pharmaceuticals and human serum. Journal of liquid chromatography & related Technologies 2002; 25(9): 1447-1456. https://doi.org/10.1081/JLC-120004759
[15] Pham-Huy C, Stathoulopoulou F, Sandouk P, Scherrmann JM, Palombo S et al. Rapid determination of valaciclovir and acyclovir in human biological fluids by high-performance liquid chromatography using isocratic elution. Journal of Chromatography B: Biomedical Sciences and Applications 1999; 732(1): 47-53. https://doi.org/10.1016/s0378-4347(99)00261-3
[16] Guideline, I. H. T. Validation of analytical procedures Q2 (R1). In International conference of harmonization. Geneva, Switzerland: 2022.
[17] https://kb.mtc-usa.com/article/molnupiravir-anp-method-with-hplc-appnote/46/?print=pdf
[18] M. Bindu, K Gandla, S Vemireddy, S Samuel and Y Praharsha. A validated stability indicating RP-HPLC method for the determination of molnupiravir in pharmaceutical dosage form. World Journal of Advanced Research and Reviews, 2022; 15(01): 580–590