QUALITY BY DESIGN APPROACH TO STABILITY-INDICATING REVERSE-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD DEVELOPMENT, OPTIMIZATION, AND VALIDATION FOR THE ESTIMATION OF SIMEPREVIR IN BULK DRUG
Objective: A simple, robust, precise, and selective stability-indicating liquid chromatography (LC) method (reverse-phase high-performance LC) was developed for the estimation of simeprevir through quality by design paradigm.
Methods: The chromatographic separation was performed on Water’s 2695(Alliance) equipped with a photodiode array detector at 300 nm. The method was developed on Discovery C18 column (250×4.6, 5 mm) using orthophosphoric acid and acetonitrile (55:45 % v/v) with the flow rate of 1 ml/min at 30°C. The degradation studies of simeprevir were carried out under the stress conditions of hydrolysis (acid, base, and neutral), oxidation, photolytic, and thermal as per the International Conference on Harmonization (ICH) guidelines. The peroxide hydrolysis shows more critical impurities which were well resolved from pure drug with the application of design of experiment and optimized the method.
Results: Independent variables (critical analytical attributes) selected for the method optimization were mobile phase ratio, flow rate, and temperature of the column based on the risk assessment. The retention time and resolution were selected as the method response. In response surface method, the central composite design and 23 factorial designs were employed for the optimization of the method. The polynomial equation was derived for the estimation of method response.
Conclusion: The method was optimized for better resolution among the drug, and impurity peaks were then validated as per the ICH parameters.
2. ICH Q8 Quality Guidance: Pharmaceutical Development; 2009.
3. A Report of World Health Organization’s on Hepatitis C virus. Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-c. [Last accessed on 2019 Mar 17].
4. Izquierdo L, Helle F, François C, Castelain S, Duverlie G, Brochot E. Review on Simeprevir for the treatment of Hepatitis C virus infection. Pharmgenomics Pers Med 2014;7:241-9.
5. Kanda T, Nakamoto S, Wu S, Yokosuka O. Review on new treatments for genotype 1 chronic hepatitis C focus on simeprevir. Ther Clin Risk Manag 2014;10:387-7.
6. Attia KA, El-Abasawi NM, El-Olemy A, Serag A. Stability-indicating HPLC-DAD method for the determination of simeprevir. Anal Chem Lett 2017;7:43-8.
7. Vanwelkenhuysen I, De Vries R, Timmerman P, Janssen TV. Determination of simeprevir: A novel, hepatitis C protease inhibitor inhuman plasma by high-performance liquid chromatography tandem mass spectrometry. J Chromatogr B 2014;958:43-4.
8. Ariaudo A, Favata F, De Nicolò A, Simiele M, Paglietti L, Boglione L, et al. A UHPLC-MS/MS method for the quantification of direct antiviral agents simeprevir, daclatasvir, ledipasvir, sofosbuvir/GS-331007,dasabuvir, ombitasvir and paritaprevir, together with ritonavir, inhuman plasma. J Pharm Biomed Anal 2016;125:369-6.
9. Nannetti G, Pagni S, Parisi SG, Alberti A, Loregian A, Palù G. Development of a simple HPLC-UV method for the determination of the Hepatitis C virus inhibitor simeprevir in human plasma. J Pharm Biomed Anal 2016;121:197-6.
10. Attia KA, El-Abasawi NM, El-Olemy A, Serag A. Different spectrophotometric methods applied for the analysis of simeprevir in the presence of its oxidative degradation product: A comparative study. Spectrochim Acta A Mol Biomol Spectrosc 2018;190:1-9.
11. Attia KA, El-Abasawi NM, El-Olemy A, Serag A. Simeprevir oxidative degradation product: Molecular modeling, in silico toxicity and resolution by synchronous spectro flourimetry. Luminescence 2017;33:1-9.
12. Zope MV, Patel RM, Patel AK, Patel SG. Development and validation of a stability indicating RP-HPLC method for the determination of potential degradation products of difluprednate in ophthalmic emulsion. Int J Pharm Pharm Sci 2018;10:79-7.
13. Prasad SN, Patel HK, Gothoskar AV. QBD-based development and evaluation of enteric coated mucoadhesive microcapsules of amoxicillin trihydrate as a novel chronotherapeutic approach for treatment of bacterial infections. Int J Pharm Pharm Sci 2018;10:90-100.
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