STABILITY INDICATING METHOD DEVELOPMENT AND VALIDATION FOR THE ESTIMATION OF PANOBINOSTAT LACTATEIN PHARMACEUTICAL DOSAGE FORMS BY UPLC
Objective: The present study aimed to develop a stability indicating ultra-performance liquid chromatography (UPLC) method for the estimation of panobinostat lactate in pharmaceutical dosage form and validate the method in accordance with ICH guidelines.
Methods: The optimized conditions for the developed UPLC method are acquity UPLC hibar C18 (100 mm × 2.1 mm, 1.8µ) column maintained at 30°C with mobile phase consisting of 0.1% ortho phosphoric acid and acetonitrile in the ratio 50:50%v/v on isocratic mode at flow rate 0.3 ml/min. The sample was detected at 266 nm.
Results: The retention time for panobinostat was found to be 1.6 min. The developed method was validated for accuracy, precision, specificity, ruggedness, robustness and solution stability. The method obeyed Beer’s law in the concentration range of 50µg/ml and 300µg/ml with correlation coefficient of 0.9998. Forced degradation studies were conducted by exposing the drug solution to various stress conditions such as acidic, basic, peroxide, neutral, photolytic and thermal conditions. The net degradation was found to be within the limits, indicating that drug is stable in stressed conditions.
Conclusion: The developed method for the estimation ofpanobinostat can be utilized for the routine analysis of pharmaceutical dosage form.
2. Revill P, Mealy N, Serradell N, Bolos J, Rosa E. Panobinostat. Drugs Future 2007;32:315.
3. Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, et al. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV 2014;1:e13.
4. Garbes L, Riessland M, Holker I, Heller R, Hauke J, Trankle Ch, et al. LBH589 induces up to 10 fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate. Hum Mol Genet 2009;18:3645–58.
5. Tate CR, Rhodes LV, Segar HC, Driver JL, Pounder FN, Burow ME, et al. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor Panobinostat. Breast Cancer Res 2012;14:R79.
6. TA Rasmussen. Comparison of HDAC inhibitors in clinical development: effect on HIV production in latently infected cells and T-cell activation. Human Vaccines Immunother 2013;9:1–9.
7. Navin Patil, Balaji Ommurugan, Karthik S Udupa, Karthik Rao. Bortezomib induced subconjunctival hemorrhage. Asian J Pharm Clin Res 2017;10:10-1.
8. Estella-Hermoso de Mendoza A, Imbuluzqueta I, Campanero MA, Gonzalez D, Vilas-Zornoza A, Agirre X, et al. Development and validation of ultra-high performance liquid chromatography-mass spectrometry method for LBH589 in mouse plasma and tissues. J Chromatogr B: Anal Technol Biomed Life Sci 2011;879:3490–6.
9. Madhavi S, Prameela Rani A. Simultaneous reverse phase ultra-performance liquid chromatography method development and validation for estimation of Grazoprevir and Elbasvir. Asian J Pharm Clin Res 2018;11:100.
10. Kishorkumar L Mule. Rapid analytical method for assay determination for prochlorperazine edisylate drug substances by Ultra performance liquid chromatography. Int J Curr Pharm Res 2017;9:118-22.
11. ICH: Q2 (R1), Validation of analytical procedures: text and methodology; 2005.
12. ICH: Q2B. Harmonized Tripartite Guideline, Validation of Analytical Procedure: Methodology, IFPMA, in: Proceedings of the International Conference on Harmonization, Geneva; 1996.
13. Ngwa G. Forced degradation studies as an integral part of HPLC stability indicating method development. Drug Delivery Technol 2010;10:56-9.