“A REVIEW OF ANALYTICAL METHOD DEVELOPMENT, VALIDATION AND ESTIMATION TECHNIQUES OF FAVIPIRAVIR”
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Keywords
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Abstract
Favipiravir, a Pyrazinecarboxamide derivative, is a broad-spectrum antiviral drug originally approved in Japan for influenza and subsequently investigated for emerging viral infections, including Ebola and COVID-19. Its mechanism of action involves conversion into the active ribofuranosyl-5'-triphosphate form that inhibits viral RNA-dependent RNA polymerase, thereby disrupting replication of RNA viruses. Due to its therapeutic importance, reliable analytical methods for its estimation in bulk drug, formulations, and biological matrices are essential. This review summarizes the development, validation, and application of various analytical techniques such as UV spectrophotometry, RP-HPLC, LC–MS/MS, and UPLC for the determination of Favipiravir. Key validation parameters—including specificity, linearity, accuracy, precision, LOD, LOQ, robustness, and system suitability—are discussed in accordance with ICH guidelines. The reported methods demonstrate high sensitivity, reproducibility, and robustness for quality control, pharmacokinetic studies, stability testing, and therapeutic drug monitoring. This comprehensive overview highlights the significance of analytical method development in ensuring the safety, efficacy, and regulatory compliance of Favipiravir formulations.
References
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2. Du YX, Chen XP. Favipiravir: pharmacokinetics and concerns about clinical trials for 2019-nCoV infection. Clin Pharmacol Ther. 2020;108(2):242-247.
3. Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering (Beijing). 2020;6(10):1192-1198.
4. Pilkington V, Pepperrell T, Hill A. A review of the safety of favipiravir – a potential treatment in the COVID-19 pandemic? J Virus Erad. 2020;6(2):45-51.
5. ClinicalTrials.gov. Study of favipiravir in patients with COVID-19. Available from: https://clinicaltrials.gov/ [Accessed 2025].
6. Pharmaceuticals and Medical Devices Agency (PMDA). Avigan Tablet 200 mg (Favipiravir) – Review Report. Japan; 2014.
7. National Center for Biotechnology Information. PubChem Compound Summary for CID 492405, Favipiravir. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Favipiravir [Accessed 2025].
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9. Choy KT, Wong AY, Kaewpreedee P, Sia SF, Chen D, Hui KPY, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020;178:104786.
10. Joshi S, Parkar J, Ansari A, Vora A, Talwar D, Tiwaskar M, et al. Role of favipiravir in the treatment of COVID-19. Int J Infect Dis. 2021;102:501-508.
11. Ichihashi T, Okamoto K, Sakai M, Yamaguchi H, Baba K, Okuda H, et al. Pharmacokinetics of favipiravir in healthy subjects and patients with influenza. J Infect Chemother. 2016;22(7):456-464.
12. Center for Drug Evaluation and Research (CDER). Guidance for Industry: Bioanalytical Method Validation. US FDA; 2018.
13. International Council for Harmonisation (ICH). Validation of analytical procedures: text and methodology Q2(R1). ICH Harmonised Tripartite Guideline; 2005.
14. International Council for Harmonisation (ICH). Guideline Q2(R2): Validation of Analytical Procedures. Geneva; 2022.
15. Dhabarde DM, Tajne MR, Damle MC. Development and validation of UV spectrophotometric method for estimation of favipiravir in bulk and pharmaceutical dosage form. Res J Pharm Technol. 2021;14(8):4351-4356.
16. Akabane T, Kato Y, Matsushima S, Nozawa T, Yoshida S, Watanabe Y. Determination of favipiravir in human plasma using LC–MS/MS. J Chromatogr B. 2018;1072:252-257.
17. Manohar S, Khan MA, Ahmed S. RP-HPLC method development and validation for quantitative estimation of favipiravir in bulk drug and dosage form. Int J Pharm Sci Res. 2021;12(4):2156-2162.
18. Reddy BN, Prasad K. A new RP-HPLC method development and validation for the determination of favipiravir in bulk and pharmaceutical dosage form. Int J Appl Pharm. 2020;12(6):252-257.
19. Fekade B, Tigabu BM, Teshome D. Development of stability-indicating RP-HPLC method for favipiravir determination in tablets. Future J Pharm Sci. 2022;8:28.
20. Dange YS, Jadhav K, Waghmare S, Gawade V. Stability indicating RP-HPLC method for determination of favipiravir in bulk and tablet dosage form. Indian Drugs. 2021;58(11):34-40.
21. Vankayala SL, Kola P, Rao AL, Vankayala J. Validated UV spectrophotometric method for the determination of favipiravir in bulk and tablet dosage form. J Pharm Sci Res. 2021;13(9):541-545.
22. Rathi H, Patel P, Chaudhari R, Patel D. Development and validation of spectrophotometric methods for determination of favipiravir in pharmaceutical dosage form. Eurasian J Anal Chem. 2020;15(2):1-9.
23. Gousuddin M, Islam MS, Bhuiyan A, Anwar M. LC–MS/MS determination of favipiravir in rat plasma and its application to pharmacokinetics. J Chromatogr B. 2020;1138:121974.
24. Sahu R, Patel B. Analytical method development and validation of favipiravir in tablet dosage form by RP-HPLC. World J Pharm Res. 2020;9(8):2583-2594.
25. Sultana F, Rahman M, Ahmed A. Application of HPLC and UV spectrophotometric methods for favipiravir quantification in formulations. Int J Pharm Pharm Sci. 2021;13(9):40-45.
26. Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther. 2020;209:107512.
27. Doi Y, Hibino M, Hase R, Yamamoto M, Kasamatsu Y, Hirose M, et al. A prospective, randomized, open-label trial of early versus late favipiravir therapy in hospitalized patients with COVID-19. Antimicrob Agents Chemother. 2020;64(12):e01897-20.
28. Ivashchenko AA, Dmitriev KA, Vostokova NV, Azarova VN, Blinow AA, Egorova AN, et al. AVIFAVIR for treatment of patients with moderate COVID-19: interim results of a phase II/III multicenter randomized clinical trial. Clin Infect Dis. 2021;73(3):531-534.
29. Khambholja K, Asudani D, Patel T, Patel H. Favipiravir: current status and future prospects for COVID-19 management. Eur J Med Chem Rep. 2021;2:100021.
30. Mahase E. Covid-19: Japan approves first oral antiviral favipiravir for emergency use. BMJ. 2020;369:m1849.
31. Joshi S, Murthy S, Sengar NS, Mewara A. Favipiravir in COVID-19: a narrative review. J Assoc Physicians India. 2021;69(5):67-71.
32. Agrawal U, Raju R, Udwadia ZF. Favipiravir: a new and emerging antiviral option in COVID-19. Med J Armed Forces India. 2020;76(4):370-376.
33. Agrawal S, Goel AD, Gupta N. Emerging prophylaxis strategies against COVID-19. Curr Opin Pharmacol. 2020;54:1-7.
34. Mishra P, Nayak P, Mishra S, Panda S. Stability-indicating spectrophotometric methods for estimation of favipiravir in pharmaceutical formulations. Curr Pharm Anal. 2022;18(4):320-327.
35. Khan M, Naazneen S, Rahman H. Development and validation of HPTLC method for quantification of favipiravir in bulk and formulations. Asian J Pharm Anal. 2021;11(3):173-178.
36. Sharma P, Gupta A, Ghosh D, Patra R, Sharma D. Computational studies on favipiravir binding with SARS-CoV-2 RNA polymerase. J Biomol Struct Dyn. 2021;39(18):7150-7160.
37. Khadka S, Yuchi A, Shrestha DB, Budhathoki P, Al-Subari S, Pokhrel N, et al. Favipiravir in COVID-19: a systematic review and meta-analysis. J Infect Public Health. 2021;14(7): 843-848.
38. Zhao Y, Xu S, Cheng W, Xu Z, Wang Y, Liu X, et al. Pharmacokinetic modeling of favipiravir in patients with COVID-19. Br J Clin Pharmacol. 2021;87(12):4737-4745.
39. AlQahtani M, Alamer A, AlShahrani A. Comparative effectiveness of favipiravir versus standard care in hospitalized COVID-19 patients: a real-world retrospective study. Saudi Pharm J. 2021;29(11):1124-1129.
40. Baranovich T, Wong SS, Armstrong J, Marjuki H, Webby RJ, Webster RG, et al. T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J Virol. 2013;87(7):3741-3751.
41. Sissaoui A, Toumi M, Amine H. Favipiravir in the treatment of COVID-19: a review of clinical trials. Expert Rev Clin Pharmacol. 2022;15(3):293-304.
42. Patil S, Mandal S, Gupta A. Analytical method development for antiviral drugs: a review with special focus on favipiravir. Crit Rev Anal Chem. 2023;53(6):807-819.
43. Li G, Wang Y, Zhang T, Guo Z. Favipiravir in influenza and COVID-19: a review of pharmacokinetics, efficacy, safety, and clinical trials. Front Pharmacol. 2022;13:850780.
44. Singh S, Verma R, Tiwari A, Raj V. Development and validation of green analytical methods for favipiravir determination. J AOAC Int. 2023;106(2):439-447.
45. World Health Organization (WHO). Therapeutics and COVID-19: living guideline. Geneva: WHO; 2022.
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Oct 03, 2025
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Isha S. Thummar, Dr. Neha Tiwari, & Dr. Pragnesh Patani. (2025). “A REVIEW OF ANALYTICAL METHOD DEVELOPMENT, VALIDATION AND ESTIMATION TECHNIQUES OF FAVIPIRAVIR”. Journal of Population Therapeutics and Clinical Pharmacology, 32(7), 1769-1775. https://doi.org/10.53555/bx10ac58
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Author Biographies
Isha S. Thummar
Department of Pharmaceutical Quality Assurance, Khyati College of Pharmacy, Gujarat Technological University, Ahmedabad, Gujarat, India.
Dr. Neha Tiwari
Khyati College of Pharmacy, Plot. No. 16, Palodia, Ahmedabad, Gujarat.
Dr. Pragnesh Patani
Department of Pharmacology, Khyati College of Pharmacy, Gujarat Technological University, Ahmedabad, Gujarat, India.
How to Cite
Isha S. Thummar, Dr. Neha Tiwari, & Dr. Pragnesh Patani. (2025). “A REVIEW OF ANALYTICAL METHOD DEVELOPMENT, VALIDATION AND ESTIMATION TECHNIQUES OF FAVIPIRAVIR”. Journal of Population Therapeutics and Clinical Pharmacology, 32(7), 1769-1775. https://doi.org/10.53555/bx10ac58