International Journal of Drug Delivery Technology
Volume 15, Issue 3

Stability-Indicating RP-HPLC Method Development and Validation for Quantification of Molnupiravir in Bulk and Pharmaceutical Formulation

Bushra Ansari1*, U A Deokate2, P B Shamkuwar1 

1Department of Pharmaceutical Chemistry, Government College of Pharmacy, Chhatrapati Sambhaji Nagar, Maharashtra, India

2Department of Pharmaceutical Chemistry, Government College of Pharmacy, Karad, Maharashtra, India 

Received: 7th Jun, 2025; Revised: 15th Jul, 2025; Accepted: 2nd Aug, 2025; Available Online: 25th Sep, 2025

ABSTRACT

The article presents the development and validation of a basic, precise, and versatile RP-HPLC technique for quantifying molnupiravir in bulk medication and capsule formulations. A Zodiac C18 column (150 × 4.6 mm, 5 μm) was used with an isocratic mobile phase comprising 15 mM ammonium acetate, acetonitrile, and methanol (70:20:10 v/v) at a flow rate of 0.8 mL/min. Detection occurred at 236 nm with a retention duration of 11.7 minutes. The technique was verified in accordance with ICH requirements for linearity, accuracy, precision, robustness, sensitivity, and system appropriateness. Linearity was detected throughout the range of 3.12–100 μg/mL, with a correlation value (R²) of 0.9999. The LOD was determined to be 2.06 μg/mL, while the LOQ was established at 6.87 μg/mL. Forced degradation experiments revealed substantial breakdown in basic and oxidative environments, although the drug remained stable in acidic and photolytic settings. The suggested approach demonstrated suitability for regular quality control and stability assessments of molnupiravir in pharmaceutical formulations.

Keywords: Molnupiravir, RP-HPLC, Stability indicating method, Method validation, Forced degradation, ICH guidelines.

How to cite this article: Bushra Ansari, U A Deokate, P B Shamkuwar. Stability-Indicating RP-HPLC Method Development and Validation for Quantification of Molnupiravir in Bulk and Pharmaceutical Formulation. International Journal of Drug Delivery Technology. 2025;15(3):1169-76. doi: 10.25258/ijddt.15.3.36

REFERENCES

  1. Kabinger F, Stiller C, Schmitzová J, Dienemann C, Kokic G, Hillen HS, et al. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol. 2021;28(9):740–6.
  2. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157.
  3. Imran M, Kumar Arora M, Asdaq SMB, Khan SA, Alaqel SI, Alshammari MK, et al. Discovery, development, and patent trends on molnupiravir: A prospective oral treatment for covid-19. Molecules. 2021;26(19).
  4. 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. N Engl J Med. 2022;386(6):509–20.
  5. Tian L, Pang Z, Li M, Lou F, An X, Zhu S, et al. Molnupiravir and Its Antiviral Activity Against COVID-19. Front Immunol. 2022;13.
  6. Bindu, Kumaraswamy Gandla, Swapna Vemireddy, Sashmitha Samuel, Yalamanchili Praharsha. A validated stability indicating RP-HPLC method for the determination of molnupiravir in pharmaceutical dosage form. World J Adv Res Rev. 2022;15(1):580–90.
  7. Perumal D, Krishnan M, Lakshmi KS. Eco-friendly Based UV Spectrophotometric Method and Analytical Quality by Design Aided Stability Indicating RP-HPLC Technique for the Estimation of Molnupiravir. Anal Chem Lett. 2023;13(2):159–73.
  8. Deshpande M, Shaikh F, Sable V, Patil K, Holam MR, Tare H. New Stability Indicating RP-HPLC Method for Estimation of the Drug Molnupiravir. Int J Pharm Qual Assur. 2023;14(1):149–58.
  9. Wagdy HA. A newly developed and validated environmentally friendly RP-HPLC stability indicating method for the COVID-19 antiviral Molnupiravir: Application to degradation kinetics structure suggestion using LC-MS and the effect on viable cells of the major degradation products. Microchem J. 2024;199.
  10. Nakka S, Gadthey S, Seema A, Marapakala K. Green Assessment of Stability Indicating RP-HPLC Method for Simultaneous Estimation of Metformin, Empagliflozin, and Linagliptin in Bulk and Fixed Dosage Forms Using AGREE and GAPI Tools. Asian J Green Chem. 2024;8(5):623–41.
  11. Swarnalatha S, Vallakeerthi N, Moorthy RS, Pingili K, Reddy PM. Development and Validation of Stability Indicating RP-HPLC Method for Simultaneous Determination of Selected Drugs Using Green Assessment in Bulk and Pharmaceutical Dosage Form. Asian J Green Chem. 2024;8(4):478–96.
  12. Chandramore KR, Sonawane SS, Ahire RS, Reddy H, Ahire SB, Jadhav PB, et al. Development and Validation of Stability Indicating LC Method for Selexipag : In-Silico Toxicity Study and Characterization of its Degradation Products. Chem Methodol. 2025;9:427–47.
  13. Elumalai S, Sharma M, Dantinapalli VLS, Palanisamy M. Novel Stability Indicating UPLC Method Development and Validation for Simultaneous Quantification of Perindopril Arginine and Bisoprolol Fumarate in Pure and Pharmaceutical Dosage Form. Adv J Chem Sect A. 2025;8(9):1488–507.
  14. Husain A. Forced Degradation Studies. J Anal Pharm Res. 2016;3(6).
  15. Deshmukh PR, Gaikwad VL, Tamane PK, Mahadik KR, Purohit RN. Development of stability-indicating HPLC method and accelerated stability studies for osmotic and pulsatile tablet formulations of Clopidogrel Bisulfate. J Pharm Biomed Anal. 2019;165:346–56.
  16. Swarnkar P, Maheshwari M. Analytical Method Validation of Compendial Hplc Method for. Int J Pharm Erud. 2021;11(03):01–11.
  17. Taleuzzaman M. Limit of Blank (LOB), Limit of Detection (LOD), and Limit of Quantification (LOQ). Org Med Chem Int J. 2018;7(5).
  18. Abass AM, Abdoon FM. Synthesis, Characterization, and Applications of Metal Oxides of ZnO, CuO, and CeO2 Nanoparticles: A Review. J Appl Organomet Chem. 2024;4(4):349–66.
  19. Prasath H, Azhakesan A, Manikandan G. Analytical Methods for Quantification of Gemcitabine in Pharmaceutical and Biological Samples : An Overview of Developments in the Last Decade. Asian J Green Chem. 2025;9:457–75.
  20. Balaji P, Khan MU. Extraction, Phytochemical Screening, Green Synthesis of Silver Nanoparticles (Ag-NPs), and Antioxidant Potential of Aphanamixis polystachya. J Appl Organomet Chem. 2025;2(1):343–67.
  21. Al-Tannak NF. UHPLC-UV method for simultaneous determination of perindopril arginine and indapamide hemihydrate in combined dosage form: A stability-indicating assay method. Sci Pharm. 2018;86(1).