Stability-Indicating Method Development and Validation for Simultaneous Estimation of Ombitasvir, Paritaprevir, and Ritonavir in Formulation by Ultra Performance Liquid Chromatography
Abstract
Aim of the present research work was to develop a sensitive, precise and robust stability-indicating UPLC method for the simultaneous estimation of ombitasvir, paritaprevir and ritonavir in formulations. The chromatographic separation of mixture of ombitasvir, paritaprevir and ritonavir was attained in isocratic method utilizing a mobile phase of 0.01N Potassium dihydrogen orthophosphate (pH 5.3) and methanol in the proportion of 60:40%v/v utilizing a BEH C18 column which has dimensions of 100 x 3 mm, 1.7m particle size and the flow rate of 0.3 ml/min. The detection system was monitored at 252nm wavelength maximum with 0.2 ml injection volume. The retaining time for ombitasvir, paritaprevir and ritonavir was achieved at 1.765 min, 2.192 min, and 1.326 min respectively. Ombitasvir, paritaprevir and ritonavir and their combined drug formulation were exposed to thermal, acidic, oxidative, photolytic, and alkaline conditions. The present method was validated as per the guidelines given by the ICH for specificity, accuracy, sensitivity, linearity and precision. The developed method was highly sensitive, rapid, precise and accurate than the earlier reported methods. The total run time was decreased to 3.0 min; hence, the technique was more precise and economical. Stability studies directed for the suitability of the technique for degradation studies of ombitasvir, paritaprevir and ritonavir. The projected method can be utilized for routine analysis in quality control department in pharmaceutical trades.
Keywords:
Ombitasvir, Paritaprevir, Ritonavir, UPLC, Stability, Validation.DOI
https://doi.org/10.25004/IJPSDR.2020.120505References
Bagaglio S, Uberti-Foppa C, Morsica G. Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017; 12:124-128.
Viekira Pak (Ombitasvir, Paritaprevir And Ritonavir Tablets; Dasabuvir Tablets), For Oral Use. Full Prescribing Information" (PDF). AbbVie Inc., North Chicago, IL 60064. Retrieved 30 July 2015. www.medicines.org.uk
Kowdley KV, Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, Everson GT, Kwo P, Foster GR, Sulkowski MS, Xie W, Pilot-Matias T, Liossis G, Larsen L, Khatri A, Podsadecki T, Bernstein B. Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1. N Engl J Med. 2014 Jan 16;370(3):222-32
Mauss, et al., eds. (2013). Hepatology 2013 a clinical textbook (PDF) (4th ed.). Düsseldorf: Flying Publisher. ISBN 978-3-924774-90-5.
Papaseit E, Vázquez A, Pérez-Mañá C, Pujadas M, De La Torre R, Farré M, Nolla J. Surviving life-threatening MDMA (3,4-methylenedioxymethamphetamine, ecstasy) toxicity caused by ritonavir (RTV). Intensive Care Medicine. 2012; 38 (7):1239–1240.
Mensing S, Eckert D, Sharma S, Polepally AR, Khatri A, Podsadecki TJ, Awni WM, Menon RM, Dutta S. Population pharmacokinetics of paritaprevir, ombitasvir, dasabuvir, ritonavir and ribavirin in hepatitis C virus genotype 1 infection: analysis of six phase III trials. British J Clin Pharmacol. 2017; 83: 527–539.
Ocque AJ, E Hagler CE, Difrancesco R, Woolwine-Cunningham Y, Bednasz CJ, Morse GD, Talal AH. Development and validation of a UPLC–MS/MS method for the simultaneous determination of paritaprevir and ritonavir in rat liver. Bioanalysis. 2016; 8(13):1353-63.
Baje SI, Jyothi B, Madhavi N. RP-HPLC Method for simultaneous estimation of ritonavir, ombitasvir and paritaprevir in tablet dosage forms and their stress degradation studies. Int J App Pharm. 2019; 11(2):193-210.
Wadie MA, Mostafa SM, El SM, Elgawish MS. Development and validation of a new, simple-Hplc method for simultaneous determination of ombitasvir, paritaprevir, ritonavir and ribavirin in tablet dosage form. Iosr journal of pharmacy and biological sciences. 2017; 12(6): 28-35.
Jahnavi B, Ganapaty S. Stability indicating RP-HPLC method development and validation for the simultaneous determination of ombitasvir, paritaprevir and ritonavir in tablet dosage forms. Asian Journal of Pharmaceutical Education and Research. 2018;7(1):90-101.
Al-Zoman NZ, Maher HM, Al-Subaie A. Simultaneous determination of newly developed antiviral agents in pharmaceutical formulations by HPLC-DAD. Chemistry Central Journal. 2017; 11(1): 2-8.
Jagadeeswaran M, Gopal N, Pavan kumar K, Siva kumar T. Quantitative Estimation of Lopinavir and Ritonavir in Tablets by RP-HPLC Method Pharmaceut Anal Acta. 2012; 3(5): 1-3.
Chiranjeevi K, Channabasavaraj KP, Lakshminarayana B, Kalyan kumar B. Development and validation of RP-HPLC method for quantitative estimation of ritonavir in bulk and pharmaceutical dosage forms. International Journal of Pharmaceutical Sciences and Research. 2011; 2(2): 336-340.
Seetaramaiah K, Anton Smith A, Ramyateja K, Alagumanivasagam G, Manavalan R. Sectrophotometric determination of ritonavir in bulk and pharmaceutical formulation. sci. Revs. Chem. Commun. 2012; 2(1): 1-6.
ICH: Q2 (R1), Validation of analytical procedures: text and methodology; 2005.
ICH: Q2B. Harmonized Tripartite Guideline, Validation of Analytical Procedure: Methodology, IFPMA, in: Proceedings of the International Conference on Harmonization, Geneva; 1996.
Trivedi CD, Mardia RB, Suhagia BN, Chauhan SP. Development and validation of spectrophotometric method for the estimation of ritonavir in tablet dosage form. International Journal of Pharmaceutical Sciences and Research. 2013; 4(12): 4567-4572.
Anjaneyulu Reddy B, Irshad Alam MD, Nazia Khanam, Radha Krishnanand P. An innovative method development and forced degradation studies for simultaneous estimation of sofosbuvir and ledipasvir by RP HPLC .International Journal of Pharmacy and Pharmaceutical Sciences. 2019;11(2): 21-26.
ICH Guidelines Q1A (R2), Stability Testing of New Drug Substances and Products, International Conference on Harmonization; 2003.
Ngwa G. Forced degradation studies as an integral part of HPLC stability indicating method development. Drug Delivery Technol. 2010;10:56-9.
Vanitha C, Reddy B, Satyanarayana SV. Quality-by-design approach to selective stability indicating RP-HPLC method development and validation of estimation of sofosbuvir in bulk drug. Int J Res Pharm Sci. 2018;9:298-308.
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