Stability-indicating high performance liquid chromatographic method for simultaneous assay of pibrentasvir and glecaprevir: Method development, validation and application to tablet dosage forms

Year 2019, Volume: 23 Issue: 3, 465 - 475, 27.06.2025

Satya Venkata Sakuntala Mamidi Lakshmana Rao Atmakuri William Carey Mamidipalli

https://izlik.org/JA39TW86ND

Abstract

Pibrentasvir and glecaprevir combination therapy acts by inhibiting RNA replication and viron assembly in hepatitis C virus. The aim and objective of the present investigation is to develop and validate a stability indicating RP-HPLC method for simultaneous quantification of pibrentasvir and glecaprevir in bulk and tablets. Pibrentasvir and glecaprevir were separated and analyzed on Agilent Eclipse column (4.6 mm × 150 mm, 5 m). The mobile phase consisted of 0.1% orthophosphoric acid and methanol (30:70, v/v), that was isocratically delivered at a flow rate of 1.0 mL/min. Retention times were 1.857 min for glecaprevir and 2.681 min for pibrentasvir. Good regression coefficients were obtained in range of 50-250 μg/mL for glecaprevir and 20–100 μg/mL for pibrentasvir. The results of validation parameters like selectivity, precision, accuracy and robustness are satisfactory. Tablet sample containing pibrentasvir and glecaprevir was subjected to degradation with 0.1N HCl, 0.1N NaOH, 30% hydrogen peroxide, thermal and photo conditions. The resulting degradants produced during the applied degradation conditions were well resolved from the peaks of pibrentasvir and glecaprevir. The utility of the proposed method was demonstrated by application to tablets containing pibrentasvir and glecaprevir combination. No interference from additives was observed. Therefore the method can be adapted in routine analysis of pibrentasvir and glecaprevir in quality control laboratories. The method can also be used for purity and degradation assessment of pibrentasvir and glecaprevir in tablets.

Keywords

Antiviral drugs , pibrentasvir , glecaprevir , stability indicating , liquid chromatography

References

• [1] Manns MP, Buti M, Gane E, Pawlotsky JM, Razavi H, Terrault N, Younossi Z. Hepatitis C virus infection. Nat Rev Dis Primers. 2017;3:17006. [CrossRef]
• [2] Bastos JCS, Padilla MA, Caserta LC, Miotto N, Vigani AG, Arns CW. Hepatitis C virus: Promising discoveries and new treatments. World J Gastroenterol. 2016;22(28):6393–6401. [CrossRef]
• [3] World Health Organization. Hepatitis C, WHO fact sheet No. 164, updated July 2015. Available from: [CrossRef]
• [4] Li HC, Lo SY. Hepatitis C virus: Virology, diagnosis and treatment. World J Hepatol. 2015;7(10):1377–1389. [CrossRef]
• [5] Lamb YN. Glecaprevir/Pibrentasvir: First global approval. Drugs. 2017;77(16):1797–1804. [CrossRef]
• [6] Forns X, Lee SS, Valdes J, Lens S, Ghalib R, Aguilar H, Felizarta F, Hassanein T, Hinrichsen H, Rincon D, Morillas R, Zeuzem S, Horsmans Y, Nelson DR, Yu Y, Krishnan P, Lin CW, Kort JJ, Mensa FJ. Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial. Lancet Infect Dis. 2017;17(10):1062–1068. [CrossRef]
• [7] Levien TL, Baker DE. Formulary drug reviews: Glecaprevir/Pibrentasvir. Hosp Pharm. 2018;53(2):75–84. [CrossRef]
• [8] Aghemo A, Colombo M. Glecaprevir/Pibrentasvir: The final piece in the Hepatitis C virus treatment puzzle? Gastroenterology. 2018;154(4):1195–1196. [CrossRef]
• [9] Ara AK, Paul JP. Novel emerging treatments for hepatitis C infection: A fast-moving pipeline. Therap Adv Gastroenterol. 2017;10(2):277–282. [CrossRef]
• [10] Hemalatha K, Kistayya C, Nizamuddhin ND, Dastiagiriamma D. Simultaneous estimation of new analytical method development and validation of glecaprevir and pibrentasvir by high performance liquid chromatography. Innovat Int J Med Pharma Sci. 2018;3(s1):5–8.
• [11] Sridevi M, Rao TS, Naidu CG. Development and validation for the simultaneous estimation of glecaprevir and pibrentasavir in drug product by UPLC. Eur J Biomed Pharm Sci. 2018;5(4):473–480.
• [12] China Babu M, Madhusudhana Chetty C, Mastanamma SK. A new force indicating RP-HPLC method development and validation for the simultaneous estimation of pibrentasvir and glecaprevir in bulk and its tablet dosage form. Pharm Methods. 2018;9(2):79–86. [CrossRef]
• [13] International Conference on the Harmonization. ICH Harmonized Tripartite Guideline. Validation of Analytical Procedures: Text and Methodology Q2 (R1), November 2005.
• [14] International Conference on the Harmonization. ICH Harmonized Tripartite Guideline. Stability Testing of New Drug Substances and Products Q1A (R2), November 2003.