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Identification and Characterization of Forced Degradation Products for Dofetilide using Rapid and Sensitive UPLC-MS/MS Method and HRMS Studies
Corresponding Author(s) : M. Ajay Babu
Asian Journal of Chemistry,
Vol. 31 No. 12 (2019): Vol 31 Issue 12
Abstract
A simple, rapid and efficient method has been developed and validated using ultra UPLC combined with Q-ToF MS system for recognition and characterization of forced degradation products obtained from dofetilide degradation studies. The dofetilide drug is an antiarrhythmic and belongs to Class III and it was treated with various stress conditions like acidic, basic, oxidative, photolytic and thermal conditions as per ICH guidelines. The main drug shows extensive degradation towards oxidative degradation conditions and single degradation product was identified through chromatogram. The chromatographic separation among main and its impurities were attained through 2.1 × 150, 1.8 μm column from gradient elution using UPLC and its detection at wavelength 230 nm. The validation was performed for the developed method using various parameters like specificity, linearity and robustness studies. Waters Synapt G2 Q TOF system was used and performed MSn studies to establish mass spectral fragmentation pathway for drug and its degradation products and determined accurate masses study. The efficiency of this method was helpful to identify and characterize the drug and degradation products using LC/MSn techniques.
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- International Conference on Harmonization, ICH Guidelines, Impurities in New Drug Substances, Topic Q3A (R2), Geneva, Switzerland (2006).
- M.A. Babu, C.V.K. Mohan, J. Satish, P.D. Kalariya, C.H.K. Raju and S.D. Mankumare, J. Appl. Pharm. Sci., 8, 65 (2018); https://doi.org/10.7324/JAPS.2018.8609.
- International Conference on Harmonization, ICH Guidelines, Stability testing of New Drug Substances and Products, Topic Q1A (R2), Geneva, Switzerland (2003).
- K.R. Chintalapati, S.K. Jagarlapudi and K.G. Sanath, New J. Chem., 42, 634 (2018); https://doi.org/10.1039/C7NJ02781H.
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References
J.P. Mounsey and J.P. DiMarco, Circulation, 102, 2665 (2000); https://doi.org/10.1161/01.CIR.102.21.2665.
N. Kaddar, S. Pilote, S. Wong and B. Caillier, J. Chromatogr. Sep. Technol., 4, 192 (2013); https://doi.org/10.4172/2157-7064.1000192.
R. Arunkumar, A. Ruckmani, L.R. Prabhu, P.G. Nayar, M. Chokkalingam, D. Rajasekaran and A.O. Arumugam, World J. Pharm. Res., 3, 511 (2014).
B. Kousar, A. Aditya, N. Charan, T.K. Vinay and B.S. Chandra Rao, J. Pharma Res., 6, 108 (2017).
K.R. Sangeetha, K.T. Ravi and M. Gandhimathi, Eur. J. Pharm. Med. Res., 4, 520 (2017).
Dofetilide USP Monograph, Version USP38/NF33, The United States Pharmacopeia, Maryland, Rockville, USA, 35, 1135 (2016).
International Conference on Harmonization, ICH Guidelines, Impurities in New Drug Substances, Topic Q3A (R2), Geneva, Switzerland (2006).
M.A. Babu, C.V.K. Mohan, J. Satish, P.D. Kalariya, C.H.K. Raju and S.D. Mankumare, J. Appl. Pharm. Sci., 8, 65 (2018); https://doi.org/10.7324/JAPS.2018.8609.
International Conference on Harmonization, ICH Guidelines, Stability testing of New Drug Substances and Products, Topic Q1A (R2), Geneva, Switzerland (2003).
K.R. Chintalapati, S.K. Jagarlapudi and K.G. Sanath, New J. Chem., 42, 634 (2018); https://doi.org/10.1039/C7NJ02781H.
International Conference on Harmonization, ICH Guidelines, Validation of Analytical Procedures: Text and Methodology, Topic Q2 (R1), Geneva, Switzerland (2005).