A Stability Indicating HPLC Method for Dronedarone in Bulk Drugs and Pharmaceutical Dosage Forms
- 1 United States Pharmacopeia-India Private Limited, Research and Development Laboratory, ICICI Knowledge Park, Turkapally, Shameerpet, Hyderabad-500 078, India
- 2 Dr. Reddy’s Laboratories Ltd. IPDO, Bachupally, Hyderabad 500049, Andhra Pradesh, India
- 3 United States Pharmacopeia-India Private Limited, Research and Development Laboratory, ICICI Knowledge Park, Turkapally, Shameerpet, Hyderabad-500 078, India
- 4 United States Pharmacopeia-India Private Limited, Research and Development Laboratory, ICICI Knowledge Park, Turkapally, Shameerpet, Hyderabad-500 078, India
- 5 United States Pharmacopeia-India Private Limited, Research and Development Laboratory, ICICI Knowledge Park, Turkapally, Shameerpet, Hyderabad-500 078, India
Abstract
The objective of the current study was to develop a validated, specific and stability-indicating reverse phase HPLC method for the quantitative determination of Dronedarone and its related substances. The determination was done for active pharmaceutical ingredient and its pharmaceutical dosage forms in the presence of degradation products, and its process-related impurities. The drug was subjected to stress conditions of hydrolysis (acid and base), oxidation, photolysis and thermal degradation per International Conference on Harmonization (ICH) prescribed stress conditions to show the stability-indicating power of the method. Significant degradation was observed during acid, oxidative and photo stress studies. In the developed HPLC method, the resolution between Dronedarone and its process-related impurities was found to be greater than 2.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.999 for Dronedarone and it’s all the five impurities. The chromatographic separation was achieved on a C8 stationary phase. The method employed a linear gradient elution and the detection wavelength was set at 288 nm. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 99.6%. The developed HPLC method was validated with respect to linearity, accuracy, precision and robustness.
- FDA “FDA Approves Multaq to Treat Heart Rhythm Disorder,” 2009.
- T. S. Mohamed Saleem, K. Bharani, C. Madhusudhana Chetty, et al., “Dronedarone in the Management of Atrial Fibrillation,” Open Access Emergency Medicine, Vol. 2010, No. 2, 2010, pp. 17-23. doi:10.2147/OAEM.S8988
- S. H. Hohnloser, H. J. G. M. Crijns, M. van Eickels, C. Gaudin, R. L. Page, C. Torp-Pedersen and S. J. Connolly, “Effect of Dronedarone on Cardiovascular Events in Atrial Fibrillation,” The New England Journal of Medicine, Vol. 360, 2009, pp. 668-678.
- R. N. Fogoros, “Dronedarone for Atrial Fibrillation, Like Amiodarone But without the Toxicity?” About.com Guide, 2011.
- N. Penugonda, A. Mohmand-Borkowski and J. F. Burke, “Dronedarone for Atrial Fibrillation: How Does It Compare with Amiodarone?” Cleveland Clinic Journal of Medicine, Vol. 78, No. 3, 2011, pp. 179-185.
- C. Xie, S. L. Yang, D. F. Zhong, X. J. Dai and X. Y. Chen, “Simultaneous Determination of Dronedarone and Its Active Metabolite Debutyldronedarone in Human Pla- sma by Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study,” Jour- nal of Chromatography B, Vol. 879, No. 28, 2011, pp. 3071-3075. doi:10.1016/j.jchromb.2011.09.004
- R. W. Bolderman, J. J. Rob Hermans and J. G. Maessen, “Determination of the Class III Antiarrhythmic Drugs Dronedarone and Amiodarone, and Their Principal Metabolites in Plasma and Myocardium by High-Perfor- mance Liquid Chromatography and UV-Detection,” Journal of Chromatography B, Vol. 877, No. 18-19, 2009, pp. 1727-1731.
- A. Patel and J. Akhtar, “RP-HPLC Method Development and Validation of Dronedarone HCl in Its Pure Form and Tablet Dosage Form,” Journal of Chemical and Pharmaceutical Research, Vol. 4, No. 4, 2012, pp. 2173-2179.
- ICH, “Stability Testing of New Drug Substances and Products Q1A (R2),” International Conference on Harmonization, IFPMA, Geneva, 2003.
- USP, United States Pharmacopoeia, “Validation of Compendial Methods,” 31st Edition, United States Pharmacopeial Convention, Rockville, 2008.
- J. T. Carstensen and C. T. Rhodes, “Drug Stability Principles and Practices,” 3rd Edition, 2000.
- M. Bakshi and S. Singh, “Development of Validated Stability-Indicating Assay Methods—Critical Review,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 28, No. 6, 2002, pp. 1011-1040. doi:10.1016/S0731-7085(02)00047-X