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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

Synthesis and Characterization of Potential and Degraded Impurities of Regadenoson

Author(s): Singaram Sathiyanarayanan*, Chidambaram Subramanian Venkatesan and Senthamaraikannan Kabilan

Volume 16, Issue 8, 2020

Page: [1130 - 1139] Pages: 10

DOI: 10.2174/1573412915666190819095255

Price: $65

Abstract

Background: Regadenoson is an A2A adenosine receptor agonist that is a coronary vasodilator and commonly used as a pharmacologic cardiac stressing agents.

Methods: HPLC method was used for the analysis of related substances. The degraded impurities during the process were isolated and characterized by IR, Mass and NMR spectral analysis.

Results: Forced degradation study of regadenoson under conditions of hydrolysis (neutral, acidic and alkaline) and oxidations suggested in the ICH Q1A(R2) was accomplished. The drug showed significant degradation under all the above conditions. On the whole, five novel degradation products were found under diverse conditions along with process related impurities which were not reported earlier.

Conclusion: All the degradation products were well characterized by using advanced spectroscopic techniques like IR, 1H NMR, 13C NMR and Mass spectra. The identification of these impurities will be productive for the quality control during the production and stability behavior of the regadenoson drug substance.

Keywords: Regadenoson, potential impurities, ICH guidelines, IR, mass, NMR, degradation products.

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[1]
Cerqueira, M.D. The future of pharmacologic stress: selective A2A adenosine receptor agonists. Am. J. Cardiol., 2004, 94(2A), 33D-40D.
[http://dx.doi.org/10.1016/j.amjcard.2004.04.017] [PMID: 15261132]
[2]
Guidance for Industry on Abbreviated New drug applications: Impurities in drug substances; Availability. Fed. Regist., 2009, 74(134), 34359-34360.
[3]
Palle, V.P.; Elzein, E.O.; Gothe, S.A.; Li, Z.; Gao, Z.; Meyer, S.; Blackburn, B.; Zablocki, J.A. Structure-affinity relationships of the affinity of 2-pyrazolyl adenosine analogues for the adenosine A2A receptor. Bioorg. Med. Chem. Lett., 2002, 12(20), 2935-2939.
[http://dx.doi.org/10.1016/S0960-894X(02)00609-1] [PMID: 12270178]
[4]
Gates, K.S. An overview of chemical processes that damage cellular DNA: spontaneous hydrolysis, alkylation, and reactions with radicals. Chem. Res. Toxicol., 2009, 22(11), 1747-1760.
[http://dx.doi.org/10.1021/tx900242k] [PMID: 19757819]
[5]
Guidance for industry Q1A(R2) Stability testing of new drug substances and products; International Conference on Harmo-nization (ICH) Guidelines: Geneva, 2003.
[6]
Stockbridge, R.B.; Schroeder, G.K.; Wolfenden, R. The rate of spontaneous cleavage of the glycosidic bond of adenosine. Bioorg. Chem., 2010, 38(5), 224-228.
[http://dx.doi.org/10.1016/j.bioorg.2010.05.003] [PMID: 20580404]
[7]
Hori, N.; Uehara, K.; Mikami, Y. Enzymatic synthesis of 5-methyluridine from adenosine and thymine with high efficiency. Biosci. Biotechnol. Biochem., 1992, 56(4), 580-582.
[http://dx.doi.org/10.1271/bbb.56.580] [PMID: 27280651]
[8]
Rios, A.C.; Yu, H.T.; Tor, Y. Hydrolytic fitness of N‐glycosyl bonds: comparing the deglycosylation kinetics of modified, alternative, and native nucleosides. J. Phys. Org. Chem., 2015, 28(3), 173-180.
[http://dx.doi.org/10.1002/poc.3318] [PMID: 25750482]
[9]
Woods, R.D.; O’Shea, V.L.; Chu, A.; Cao, S.; Richards, J.L.; Horvath, M.P.; David, S.S. Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases. Nucleic Acids Res., 2016, 44(2), 801-810.
[http://dx.doi.org/10.1093/nar/gkv1469] [PMID: 26673696]
[10]
Berti, P.J.; McCann, J.A.B. Toward a detailed understanding of base excision repair enzymes: transition state and mechanistic analyses of N-glycoside hydrolysis and N-glycoside transfer. Chem. Rev., 2006, 106(2), 506-555.
[http://dx.doi.org/10.1021/cr040461t] [PMID: 16464017]

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