Development and validation of HPTLC method for estimation of dofetilide in pharmaceutical dosage form and determination of its degradation profile by MS-MS method

Yıl 2020, Cilt: 50 Sayı: 2, 71 - 78, 27.08.2020

Ritesh Bhole Khandu Chadar Yogesh Zambare Chandrakant G. Bonde

Öz

Background: Dofetilide is the class III antiarrhythmic drug used as a potassium channel blocker approved by US FDA in 1999 for the maintenance of sinus rhythm in individuals prone to atrial flutter and atrial fabrication. Currently there is no HPTLC-MS method reported for systematic characterization of degradation products dofetilide. Methods: As per the ICH guidelines, the HPTLC method for the determination of dofetilide both in bulk and pharmaceutical formulation has been developed and validated. The degradation products were identified and characterized by using MS/MS. The Rf value was found to be 0.52±0.3. The degradation study was performed as per ICH guidelines (Q2R1). Isolation of the degradation product by HPTLC method and categorized by MS/MS method. Results: The linearity of the method was found suitable over the range 100-600 ng/band with r2 of 0.998. Dofetilide was subjected to stability studies, the drug was found to degrade under various stress conditions. The recovery was found in the range of 98-101%. HPTLC-MS/MS method showed a possible degradation mechanism of 7 degrading products. The degradation of the drug under various stress conditions indicates the storage conditions for the drug and drug product during its shelf life. Conclusion: The HPTLC method developed for its linearity, range, precision studies, LOD and LOQ can be used for the routine quality control of the drug dofetilide in bulk drugs. The degradation pathway of a drug can help in the future to identify the impurities and for the impurity profiling of dofetilide.

Anahtar Kelimeler

Stability indicating, HPTLC, HPTLC-MS/MS degradation studies, dofetilide

Kaynakça

• Al-Dashti, R., & Sami, M. (2001). Dofetilide: A new class III antiarrhythmic agent. The Canadian Journal of Cardiology, 17(1), 63–67.
• Aktas, M. K., Shah, A. H., & Akiyama, T. (2007). Dofetilide-induced long QT and torsades de pointes. Annals of Noninvasive Electrocardiology, 12, 197–202.
• Bhole, R. P., Biradar, P., & Bonde, C. G. (2018). Development and validation of stability indicating HPTLC method for estimation of dasatinib and characterization of degradation products by using mass spectroscopy. Eurasian Journal of Analytical Chemistry, 13(4), 1–11.
• Bhole, R. P., Naksarkhre, S., & Bonde, C. G. (2019). A stability indicating HPTLC method for apremilast and identification of degradation products using MS/MS. Journal of Pharmaceutical Sciences and Research, 11(5), 1861–1869.
• Bhole, R. P., Zombade, T., Bonde, C. G., & Zambare, Y. B. (2019). Identification and characterization of degradation products by using Ms-Ms studies for developed and validated stability indicating HPTLC method for estimation of Nintedanib Esylate in pharmaceutical dosage form. Eurasian Journal of Analytical Chemistry, 14(2), 60–70.
• Bhole, R. P., Shinde, S. S., Chitlange, S. S., & Wankhede, S. B. (2015). A high-performance thin layer chromatography (HPTLC) method for simultaneous determination of diphenhydramine hydrochloride and naproxen sodium in tablets. Analytical Chemistry Insights, 10, 47–51.
• Bonthagarala, B., Ch, P. K. (2003). Formulation and evalution of lansoprazole delayed release. Journal of Pharma Research, 6, 108–114.
• Bhole, R. P., & Tamboli, F. (2018). Development and validation of stability indicating HPTLC-MS method for estimation of empagliflozin in pharmaceutical dosage form. Analytical Chemistry Letters, 8(2), 244–256.
• Clusin, W. T. (2003). Calcium and cardiac arrhythmias: DADs, EADs, and alternans. Critical Reviews in Clinical Laboratory Sciences, 40, 337–375.
• Chi, Z., Liu, R., & Wang, K. (2017). A sensitive and rapid LC–MS-MS method for simultaneous determination of propafenone and its active metabolite 5-Hydroxypropafenone in human plasma and its application in a pharmacokinetic study. Journal of Chromatographic Science, 55(9), 911–917.
• Ceresole, R., Moyano, M. A., Pizzorno, M. T., & Segall, A. (2007). Validated reversed phase HPLC method for the determination of atenolol in the presence of its major degradation product. Journal of Liquid Chromatography & Related Technologies, 29(20), 3009–3019.
• Fegade, J. D., Bhole, R. P., Patil, V. R., & Chaudhari, R.Y. (2009). Development and validation of reverse phase high performance liquid chromatographic method for simultaneous estimation of paracetamol and piroxicam in tablet. International Journal of PharmTech Research, 1(2),184–190.
• (2005) ICH HARMONISED TRIPARTITE GUIDELINE, https://www. ich.org/fileadmin/Public. Accessed on 04/05/2019.
• Jadhav, S. A., Nimbalkara, K. P., Mathad, V. T., & Mali, A. C. (2013). Stability indicating RP-HPLC method for the determination of dronedarone hydrochloride and its potential process-related impurities in bulk drug and pharmaceutical dosage form. American Journal of Analytical Chemistry, 4(6), 323–335.
• Krafte, D. S., & Volberg, W. A. (1994). Voltage dependence of cardiac delayed rectifier block by methanesulfonamide class III antiarrhythmic agents. Journal of Cardiovascular Pharmacology, 23, 37–41.
• Kaddar, N., Pilote, S., Wong, S., Caillier, B., & Patoine, D. (2013). Simultaneous determination of dofetilide and amlodipine in plasma by HPLC. Journal of Chromatography and Separation Techniques, 4(6), 192.
• Mounsey, J. P., & DiMarco, J. P. (2007). Cardiovascular drugs. Dofetilide. Circulation, 102, 2665–2670.
• Qile, M., Henriett, D. M., & David, S. (2019). LUF7244, an allosteric modulator/activator of Kv11.1 channels, counteracts dofetilide induced torsades de pointes arrhythmia in the chronic atrioventricular block dog model. British Journal of Pharmacology, 176, 3871–3885.
• Rakibe, U., Tiwari, R., Mahajan, A., Rane, V., & Wakte, P. (2018). LC and LC–MS/MS studies for the identification and characterization of degradation products of acebutolol. Journal of Pharmaceutical Analysis, 8(6), 357–365.
• Shivashankar, V., & Gandhimathi, M. (2005). RP-HPLC method development and validation for the analyisis of dronedarone hydrochloride in tablet dosage form. Journal of Pharmacreations, 2(4), 66–71.
• Udin, E. F., Sung, S., Hunge, K. M., & Hu, S. (2019). Development and validation of a UPLC-MS/MS analytical method for dofetilide in mouse plasma and urine, and its application to pharmacokinetic study. Journal Of Pharmaceutical And Biomedical Analysis, 172, 183–188.
• Woolf, V. A., Miler, D. G., & Gosting, L. J. (1962). Isothermal diffusion measurements on the system H2O-Glycine-KCl at 25; Tests of the onsager reciprocal relation. Journal of American Chemical Society, 84(3), 317–331.
• Wells, R., Khairy, P., Harris, L., Anderson, C. C., & Balaji, S. (2009). Dofetilide for atrial arrhythmias in congenital heart disease: A multicenter study. Pacing and clinical electrophysiology, 32, 1313– 1318.