Molnupiravir detection by tandem mass spectrometry

Duygu Eryavuz Onmaz; Fatma Hümryra Yerlikaya; Mustafa Onmaz

doi:10.47482/acmr.1397265

EN

Molnupiravir detection by tandem mass spectrometry

Abstract

Background: After the COVID-19 epidemic that broke out in 2019, studies on antiviral drugs accelerated. In clinical studies with both re-purposed drugs and newly discovered drugs, the need for reliable methods that allow the measurement of drug levels in the blood has increased. Molnupiravir is one of the drugs considered under the treatment of COVID-19 and is on the agenda with conflicting findings. However, there are limited validated methods that report the measurement of molnupiravir levels. Therefore, our aim in this study was to develop a practical, robust validated tandem mass spectrometric method that allows the measurement of molnupiravir levels. Methods: Method development studies for the measurement of molnupiravir levels were performed with a liquid chromatography-tandem mass spectrometry (LC-MS / MS) device and the method was validated according to CLSI (The Clinical & Laboratory Standards Institute) protocols. Linearity, recovery, precision, stability, matrix effect, carry-over and lower limit determination studies were performed. Results: The method was linear with a correlation coefficient value of 0.993 in the range of 20 ng/mL-20 µg/mL. The sensitivity of the method was 20 ng/mL. The CV% obtained from the intra- and inter-assay studies was below 6.2% and the mean recovery was over 95%. Total analysis time was 5 minutes for each sample. Conclusions: A simple, cost-effective, reliable tandem mass spectrometric method with high sensitivity and accuracy based on protein precipitation alone has been developed for the measurement of molnupiravir levels.

Keywords

COVID-19 , molnupiravir , pandemic , tandem mass spectrometry , drug monitoring

References

Chang D, Chang X, He Y, Tan KJK. The determinants of COVID-19 morbidity and mortality across countries. Sci Rep 2022;12(1):5888.
Rahmah L, Abarikwu SO, Arero AG, Essouma M, Jibril AT, Fal A, et al. Oral antiviral treatments for COVID-19: opportunities and challenges. Pharmacol Rep 2022;74(6):1255-78.
Mali KR, Eerike M, Raj GM, Bisoi D, Priyadarshini R, Ravi G, et al. Efficacy and safety of Molnupiravir in COVID-19 patients: a systematic review. Ir J Med Sci (1971) 2023;192(4):1665-78.
Ng TI, Correia I, Seagal J, DeGoey DA, Schrimpf MR, Hardee DJ, et al. Antiviral drug discovery for the treatment of COVID-19 infections. Viruses. 2022;14(5):961.
Li G, Hilgenfeld R, Whitley R, De Clercq E. Therapeutic strategies for COVID-19: progress and lessons learned. Nat Rev Drug Discov 2023;22(6):449-75.
Zarenezhad E, Marzi M. Review on molnupiravir as a promising oral drug for the treatment of COVID-19. Med Chem Res 2022;31(2):232-43.
Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients.
Butler CC, Hobbs FDR, Gbinigie OA, Rahman NM, Hayward G, Richards DB, et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 2023;401(10373):281-93.
Malin JJ, Weibel S, Gruell H, Kreuzberger N, Stegemann M, Skoetz N. Efficacy and safety of molnupiravir for the treatment of SARSCoV- 2 infection: a systematic review and meta-analysis. J Antimicrob Chemother 2023;78(7):1586-98.
Focosi D. Molnupiravir: From hope to epic fail? Viruses. 2022;14(11):2560.

M. Annadi A, Zahar N, Abdel-Sattar N, Mohamed E, Mahmoud S, Attia M. Development and validation of molnupiravir assessment in bulk powder and pharmaceutical formulation by the RP-HPLC-UV method. RSC Adv. 2022;12(53):34512-19.
Sharaf YA, El Deeb S, Ibrahim AE, Al-Harrasi A, Sayed RA. Two green micellar HPLC and mathematically assisted UV spectroscopic methods for the simultaneous determination of molnupiravir and favipiravir as a novel combined COVID-19 antiviral regimen. Molecules. 2022;27(7):2330.
Saraya RE, Deeb SE, Salman BI, Ibrahim AE. Highly sensitive highperformance thin-layer chromatography method for the simultaneous determination of molnupiravir, favipiravir, and ritonavir in pure forms and pharmaceutical formulations. J Sep Sci 2022;45(14):2582-90.
Gouda AS, Marzouk HM, Rezk MR, Salem AM, Morsi MI, Nouman EG, et al. A validated LC-MS/MS method for determination of antiviral prodrug molnupiravir in human plasma and its application for a pharmacokinetic modeling study in healthy Egyptian volunteers. J Chromatogr B Analyt Technol Biomed Life Sci 2022;1206:123363.
Amara A, Penchala SD, Else L, Hale C, FitzGerald R, Walker L, 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. J Pharm Biomed Anal 2021;206:114356.74
Parsons TL, Kryszak LA, Marzinke MA. Development and validation of assays for the quantification of β-D-N(4)-hydroxycytidine in human plasma and β-D-N(4)-hydroxycytidine-triphosphate in peripheral blood mononuclear cell lysates. J Chromatogr B Analyt Technol Biomed Life Sci 2021;1182:122921.
Çamlik G, Beyazaslan F, Kara E, Ulker D, Albayrak I, Degim İ. A Validated High-Pressure Liquid Chromatography (HPLC) Method for Molnupiravir. Medical Research Archives 2022;10(9):1-9.
Wayne PA, CLSI document C62-A. Clinical and Laboratory Standards Institute, Liquid Chromatography-Mass Spectrometry Methods; Approved Guidelines, Pennsylvania, USA, 2014.
Meesters RJ and Voswinkel S. Bioanalytical method development and validation: from the USFDA 2001 to the USFDA 2018 guidance for industry. J Appl Bioanal 4(3), 67-73
Chambers E, Wagrowski-Diehl DM, Lu Z, Mazzeo JR. Systematic and comprehensive strategy for reducing matrix effects in LC/MS/MS analyses. J Chromatogr B Analyt Technol Biomed Life Sci 2007;852(1- 2):22-34.
Gao Y, Liu M, Li Z, Xu J, Zhang J, Tian J. Molnupiravir for treatment of adults with mild or moderate COVID-19: a systematic review and meta-analysis of randomized controlled trials. Clin Microbiol Infect 2023;29(8):979-99.
Reçber T, Timur SS, Erdoğan Kablan S, Yalçın F, Karabulut TC, Neslihan Gürsoy R, et al. A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies. J Pharm Biomed Anal 2022;214:114693.
Yuan YS, Liao JM, Kang CM, Li BL, Lei XR, Yu KW, et al. A simple and accurate LC‑MS/MS method for monitoring cyclosporin A that is suitable for high throughput analysis. Exp Ther Med 2023;26(1):342.
Annadi AM, El Zahar NM, Abdel-Sattar NA, Mohamed EH, Mahmoud SA, Attia MS. Development and validation of molnupiravir assessment in bulk powder and pharmaceutical formulation by the RP-HPLC-UV method. RSC Adv. 2022;12(53):34512-19.
Reçber T, Timur SS, Kablan SE, Yalçın F, Karabulut TC, Gürsoy RN, Eroğlu H, Kır S, Nemutlu E. A stability indicating RP-HPLC method for determination of the COVID-19 drug molnupiravir applied using nanoformulations in permeability studies. J Pharm Biomed Anal. 2022;214:114693.
Sharaf YA, El Deeb S, Ibrahim AE, Al-Harrasi A, Sayed RA. Two green micellar HPLC and mathematically assisted UV spectroscopic methods for the simultaneous determination of molnupiravir and favipiravir as a novel combined COVID-19 antiviral regimen. Molecules. 2022;27(7):2330.

Details

Primary Language

English

Subjects

Clinical Chemistry

Journal Section

Research Article

Authors

Duygu Eryavuz Onmaz ^*
0000-0001-8564-1824
Türkiye

Fatma Hümryra Yerlikaya
0000-0002-4107-5389
Türkiye

Mustafa Onmaz
0000-0002-1962-9357
Türkiye

Publication Date

May 31, 2024

Submission Date

November 28, 2023

Acceptance Date

March 1, 2024

Published in Issue

Year 2024 Volume: 5 Number: 2

DOI

https://doi.org/10.47482/acmr.1397265

IZ

https://izlik.org/JA94UC34WA

APA

Eryavuz Onmaz, D., Yerlikaya, F. H., & Onmaz, M. (2024). Molnupiravir detection by tandem mass spectrometry. Archives of Current Medical Research, 5(2), 66-74. https://doi.org/10.47482/acmr.1397265

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Molnupiravir detection by tandem mass spectrometry

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Molnupiravir detection by tandem mass spectrometry

Abstract

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References

Details

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Acceptance Date

Published in Issue

DOI

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