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Separation of Empagliflozin and its Impurities by Validated Stability Indicating HPLC Method and LC-MS Characterization of Oxidative Degradation Product
Corresponding Author(s) : Sunkara Bhawani
Asian Journal of Chemistry,
Vol. 35 No. 6 (2023): Vol 35 Issue 6, 2023
Abstract
The HPLC assay strategy for two impurities (EPN-R-ISO impurity and the EPN-Diol impurity) which are related to empagliflozin synthesis was designed and verified for the reliable measurement of EPN-R-ISO and EPN-Diol impurities in empagliflozin bulk APIs. The chromatographical EPN-R-ISO and the EPN-Diol impurities analysis was done on Discovery C18 stationery column with isocratic type mobile phase exploited was potassium dihydrogenphosphate (0.01 M, pH calibrated to 2.0 by phosphoric acid) and acetonitrile in 70%:30% v/v ratio and injected at a flow measure of 1.0 mL/min. The degradation of empagliflozin under stressful conditions such as acid generated hydrolysis, base generated hydrolysis, peroxide generated oxidation, thermal generated degradation and UV generated hydrolysis was also included. The method established was verified for precision (0.0837% RSD for EPN-R-ISO; 0.1831% RSD for EPN-Diol), sensitivity (LOD: 0.030262 ppm EPN-R-ISO concentration, 0.031873 ppm EPN-Diol concentration; LOQ: 0.092621 ppm EPN-R-ISO concentration, 0.09755 ppm EPN-Diol concentration), linearity (0.1 ppm to 90.0 ppm concentration of both EPN-R-ISO and EPN-Diol) and accuracy (95.07% to 96.27% EPN-R-ISO recovery; 97.72% to 100.03% EPN-Diol recovery).
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- J.E. Frampton, Drugs, 78, 1037 (2018); https://doi.org/10.1007/s40265-018-0937-z
- M.J. Levine, Curr. Diabetes Rev., 13, 405 (2017); https://doi.org/10.2174/1573399812666160613113556
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- E.P. Commission, The European Pharmacopoeia, Council of Europe European directorate for the quality of Medicines, Strasbourg, France (2016).
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- M.M. Mabrouk, S.M. Soliman, H.M. El-Agizy and F.R. Mansour, BMC Chem., 13, 83 (2019); https://doi.org/10.1186/s13065-019-0604-9
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References
J.E. Frampton, Drugs, 78, 1037 (2018); https://doi.org/10.1007/s40265-018-0937-z
M.J. Levine, Curr. Diabetes Rev., 13, 405 (2017); https://doi.org/10.2174/1573399812666160613113556
H.U. Haering, L. Merker, A.V. Christiansen, F. Roux, A. Salsali, G. Kim, T. Meinicke, H.J. Woerle and U.C. Broedl, Diabetes Res. Clin. Pract., 110, 82 (2015); https://doi.org/10.1016/j.diabres.2015.05.044
B.K. Irons and M.G. Minze, Diabetes Metab. Syndr. Obes., 7, 15 (2014); https://doi.org/10.2147/DMSO.S38753
A.Y. Abdin, P. Yeboah and C. Jacob, Int. J. Environ. Res. Public Health, 17, 1030 (2020); https://doi.org/10.3390/ijerph17031030
S. Ozawa, H.H. Chen, Y.A. Lee, C.R. Higgins and T.T. Yemeke, Am. J. Trop. Med. Hyg., 106, 1778 (2022); https://doi.org/10.4269/ajtmh.21-1123
ICH Quality Guideline, Impurities in new drug substances Q3A (R2), in Proceedings of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuti cals for Human Use, vol. 25, Geneva, Switzerland (2006).
European Medicines Agency, Q3B (R2) Impurities in New Drug Products, vol. 4, European Medicines Agency, London, UK (2006).
P. Borman and D. Elder, Q2 (R1) Validation of Analytical Procedures: Text and Methodology, in ICH Quality Guidelines, Wiley, Hoboken, NJ, USA (2005).
E.P. Commission, The European Pharmacopoeia, Council of Europe European directorate for the quality of Medicines, Strasbourg, France (2016).
X. Wang, L. Zhang, D. Byrne, L. Nummy, D. Weber, D. Krishnamurthy, N. Yee and C.H. Senanayake, Org. Lett., 16, 4090 (2014); https://doi.org/10.1021/ol501755h
M. Hrapchak, B. Latli, X.J. Wang, H. Lee, S. Campbell, J.J. Song and C.H. Senanayake, J. Labelled Comp. Radiopharm., 57, 687 (2014); https://doi.org/10.1002/jlcr.3240
Guidance for Industry Q3A (R2), Impurities in New Drug Substances, In: Proceedings of the International Conference on Harmonization, Geneva (2008).
J.W. Manoel, G.B. Primieri, L.M. Bueno, N.R. Wingert, N.M. Volpato, C.V. Garcia, E.E. Scherman Schapoval and M. Steppe, RSC Adv., 10, 7313 (2020); https://doi.org/10.1039/C9RA08442H
S.H. Jaiswal, World J. Pharm. Res., 6, 1025 (2017); https://doi.org/10.20959/wjpr20177-8741
H. Wen-jing, Z. Tao, H. Hua, C. Hao and Z. Xiao-dong, Chinese J. Pharma. Anal., 36, 902 (2016).
M.M. Mabrouk, S.M. Soliman, H.M. El-Agizy and F.R. Mansour, BMC Chem., 13, 83 (2019); https://doi.org/10.1186/s13065-019-0604-9
N. Patel and S. Patel, Res. J. Pharm. Tech., 14, 4595 (2021); https://doi.org/10.52711/0974-360X.2021.00799
A.T. da Silva, G.R. Brabo, D.S. Porto, J. da Silva Jonco, L. Bajerski, F.R. Paula and C.S. Pai, J. Chromatogr. Sci., bmac106 (2022); https://doi.org/10.1093/chromsci/bmac106
International Conference on the Harmonization. ICH Stability Testing of New Drug Substances and Products Q1A (R2), Geneva (2003).
International Conference on the Harmonization. ICH Harmonized Tripartite Guideline. Validation of Analytical Procedures: Text and Methodology Q2(R1), Geneva (2005).