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Synthesis and Characterization of Potential Impurities of Eltrombopag Olamine
Corresponding Author(s) : Katuroju Srinivasachary
Asian Journal of Chemistry,
Vol. 33 No. 1 (2021): Vol 33 Issue 1
Abstract
This work reports the feasibility of recently developed industrial viable process for eltrombopag olamine starting from 2-bromo-6-nitro phenol and reports the identification of four potential impurities related to eltrombopag olamine, namely eltrombopag olamine ester (1), 2-aminophenol analogue of eltrombopag (2), 3,3′-(2-amino-3-oxo-3H-phenoxazine-4,6-diyl dibenzoic acid (3), 2′-hydroxy[1,1-biphenyl]-3-carboxylic acid (4). These impurities are the crucial components in determining the quality of the drug substance, eltrombopag olamine during its manufacturing. These impurities have impact on the quality of eltrombopag olamine and controlled these impurities results excellent yields of active pharma ingredient of eltrombopag olamine.
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- C.B. Burness, Drugs, 74, 1961 (2014); https://doi.org/10.1007/s40265-014-0312-7
- P. Lee, H. Aizawa, L. Gan, C. Prakash and D. Zhong, Eltrombopag, In: Handbook of Metabolic Pathways of Xenobiotics, Wiley, vol. 3, pp1299-1301 (2014).
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- K.J. Duffy, C. Erickson-Miller, J. Jenkins, J.I. Luengo and S. Visonneau, Thrombopoietin Mimetics, US Patent US 7,473,686B2 (2000).
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- International Conference on Harmonization (ICH) Guidelines. Q2B Validation of Analytical Procedures: Methodology; ICH Guildelines: Geneva, Switzerland (1996).
- International Conference on Harmonization (ICH) Guidelines Q3A(R): Impurities in New Drug substances; ICH Guidelines: Geneva, Switzerland (2002).
- H. Sharghi and M.H. Sarvari, Tetrahedron, 59, 3627 (2003); https://doi.org/10.1016/S0040-4020(03)00518-0
- S. Mukherjee, S. Roy, S. Mukherjee and B. Biswas, J. Mol. Struct., 1217, 128348 (2020); https://doi.org/10.1016/j.molstruc.2020.128348
- S. Tingting, A Kind of Preparation Method for the Medicine Eltrombopag Olamine for being used to Treat Idiopathic Thrombocytopenic Purpura, Chinese Patent CN 107915678A (2017).
- V.K. Agarwal, L.K. Katariya, G.B. Patel and H.S. Patel, Process for the Preparation of Eltrombopag Olamine, Patent WO 2017081014A1(2016).
- S.J. Desai, S.P.D. Dwivedi, M.L. Rupapara and D.M. Keshavala, Processes for the Preparation of Eltrombopag and Pharmaceutically Acceptable Salts, Solvates and Intermediates Thereof, Patent WO2015111085 A2 (2015).
- V.R.M. Moturu, S. Tiwari, S.K. Nadakudity, B. Samala, C. Rajesh, K.S. Chary and M. Sivakumaran, An Improved Process for the Preparation of Eltrombopag Olamine and its Intermediates, Indian Patent IN201841020662A (2019).
- B.P. Reddy, K.R. Reddy, J.S. Reddy and B.V. Krishna, Crystalline form of Eltrombopag Free Acid, Patent WO 2016/035018A1 (2015).
- V.R.M. Moturu, S. Tiwari, S.K. Nadakudity, B. Samala, C. Rajesh, K.S. Chary and M. Sivakumaran, Novel Salts of Eltrombopag and Process for the Preparation Thereof, Indian Patent IN 201841008924A (2019).
- X.J. Jiang, X. Zhang, M. Zhou and Y.X. Meng, A Kind of Preparation Method of Eltrombopag Olamine, Chinese Patent CN 109096195A(2018).
- H. Xu, X. Wu and J. Cen, Eltrombopag Intermediate and Preparation Method therefor and Application thereof, Chinese Patent CN105085276 A (2015).
- M. Meng, S. Ruiping, Y. Yuanyuan and C. Zongliang, A Kind of Preparation Method of Ai Qu Pools Pa, Chinese Patent CN 108033914 (2018).
- P. Revill, N. Serradell and J. Bolos, Drugs Future, 31, 767 (2006); https://doi.org/10.1358/dof.2006.031.09.1030939
References
C.B. Burness, Drugs, 74, 1961 (2014); https://doi.org/10.1007/s40265-014-0312-7
P. Lee, H. Aizawa, L. Gan, C. Prakash and D. Zhong, Eltrombopag, In: Handbook of Metabolic Pathways of Xenobiotics, Wiley, vol. 3, pp1299-1301 (2014).
A. Avdagic and P.S. Baran, Processes for the Preparation of an Intermediate in the Synthesis of Eltrombopag, Patent WO 2013049605A1 (2013).
K.J. Duffy, C. Erickson-Miller, J. Jenkins, J.I. Luengo and S. Visonneau, Thrombopoietin Mimetics, US Patent US 7,473,686B2 (2000).
D.M. Basha, G.V. Reddy, T.S. Rani, E. Susithra and R. Chekkara, Asian J. Chem., 27, 4615 (2015). https://doi.org/10.14233/ajchem.2015.19252
International Conference on Harmonization (ICH) Guidelines. Q2B Validation of Analytical Procedures: Methodology; ICH Guildelines: Geneva, Switzerland (1996).
International Conference on Harmonization (ICH) Guidelines Q3A(R): Impurities in New Drug substances; ICH Guidelines: Geneva, Switzerland (2002).
H. Sharghi and M.H. Sarvari, Tetrahedron, 59, 3627 (2003); https://doi.org/10.1016/S0040-4020(03)00518-0
S. Mukherjee, S. Roy, S. Mukherjee and B. Biswas, J. Mol. Struct., 1217, 128348 (2020); https://doi.org/10.1016/j.molstruc.2020.128348
S. Tingting, A Kind of Preparation Method for the Medicine Eltrombopag Olamine for being used to Treat Idiopathic Thrombocytopenic Purpura, Chinese Patent CN 107915678A (2017).
V.K. Agarwal, L.K. Katariya, G.B. Patel and H.S. Patel, Process for the Preparation of Eltrombopag Olamine, Patent WO 2017081014A1(2016).
S.J. Desai, S.P.D. Dwivedi, M.L. Rupapara and D.M. Keshavala, Processes for the Preparation of Eltrombopag and Pharmaceutically Acceptable Salts, Solvates and Intermediates Thereof, Patent WO2015111085 A2 (2015).
V.R.M. Moturu, S. Tiwari, S.K. Nadakudity, B. Samala, C. Rajesh, K.S. Chary and M. Sivakumaran, An Improved Process for the Preparation of Eltrombopag Olamine and its Intermediates, Indian Patent IN201841020662A (2019).
B.P. Reddy, K.R. Reddy, J.S. Reddy and B.V. Krishna, Crystalline form of Eltrombopag Free Acid, Patent WO 2016/035018A1 (2015).
V.R.M. Moturu, S. Tiwari, S.K. Nadakudity, B. Samala, C. Rajesh, K.S. Chary and M. Sivakumaran, Novel Salts of Eltrombopag and Process for the Preparation Thereof, Indian Patent IN 201841008924A (2019).
X.J. Jiang, X. Zhang, M. Zhou and Y.X. Meng, A Kind of Preparation Method of Eltrombopag Olamine, Chinese Patent CN 109096195A(2018).
H. Xu, X. Wu and J. Cen, Eltrombopag Intermediate and Preparation Method therefor and Application thereof, Chinese Patent CN105085276 A (2015).
M. Meng, S. Ruiping, Y. Yuanyuan and C. Zongliang, A Kind of Preparation Method of Ai Qu Pools Pa, Chinese Patent CN 108033914 (2018).
P. Revill, N. Serradell and J. Bolos, Drugs Future, 31, 767 (2006); https://doi.org/10.1358/dof.2006.031.09.1030939