Semi-preparative isolation and characterization of a principal oxidative degradation product in galantamine hydrobromide by LC-ESI-MSn and 2D-NMR

• Autorzy: Thomas, S. , Paul, S. K. , Agarwal, A. , Mathela, C. S.
• Języki publikacji: EN

Abstrakty

EN

Galantamine hydrobromide was subjected to oxidative stress degradation using hydrogen peroxide and analyzed as per the chromatographic conditions described in European Pharmacopoeia. The drug showed considerable degradation at ambient temperature resulting in the formation of two degradation products at relative retention times (RRTs) 0.63 and 2.52. The minor degradant at RRT 0.63 was identified as galantamine N-oxide. The principal degradant formed at RRT 2.52 was found to be unknown and has not been reported previously. The unknown impurity was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by isolation using semi-preparative high-performance liquid chromatography (HPLC). The isolated impurity was characterized using one-dimensional, two-dimensional nuclear magnetic resonance spectroscopy (1D and 2D NMR) and elemental analysis (EA). The principal degradant was found to be formed due to the generation of bromine and subsequent attack on the aromatic ring via in situ reaction between hydrogen bromide and hydrogen peroxide. The unknown impurity was characterized as (4aS,6R,8aS)-5,6,9,10,11,12-hexahydro-1-bromo-3-methoxy-11-methyl-4aH-[1]benzofuro [3a,3,2-ef] [2] benzazepin-6-ol.

Słowa kluczowe

EN

galantamine hydrobromide; oxidative degradation; LC-MS/MS; 2D NMR

• Czasopismo: Acta Chromatographica
• Rocznik: 2014
• Tom: Vol. 26, no. 3
• Strony: 429--438
• Opis fizyczny: Bibliogr. 20 poz., rys., tab.

Twórcy

autor

Thomas, S.

• Jubilant Life Sciences Ltd. Analytical Research Department R&D Centre, C-26, Sector-59 Noida Uttar Pradesh 201 301 India,

autor

Paul, S. K.

• Jubilant Life Sciences Ltd. Analytical Research Department R&D Centre, C-26, Sector-59 Noida Uttar Pradesh 201 301 India

autor

Agarwal, A.

• Jubilant Life Sciences Ltd. Analytical Research Department R&D Centre, C-26, Sector-59 Noida Uttar Pradesh 201 301 India

autor

Mathela, C. S.

• Kumaun University Department of Chemistry DSB Campus Nainital Uttarakhand 263 001 India

Bibliografia

• [1] S. Lilienfeld, Galantamine-a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer’s disease, CNS Drug Rev., 8, 159 (2002).
• [2] A. Maelicke, A. Schrattenholz, M. Samochocki, M. Radina, and E.X. Albuquerque, Behav. Brain Res., 113, 199 (2000).
• [3] Y.H. Hsieh, Y.H. Yang, H.H. Yeh, P.C. Lin, and S.H. Chen, Electrophoresis, 30, 644 (2009).
• [4] R. Mol, E. Kragt, I. Jimidar, G.J. de Jong, and G.W. Somsena, J. Chromatogr., B, 843, 283 (2006).
• [5] A. Rizzi, R. Schuh, A. Bruckner, B. Cvitkovich, L. Kremser, U. Jordis, J. Frohlich, B. Kuenburg, and L. Czollner, J. Chromatogr., B, 730, 167 (1999).
• [6] H.A. Claessens, M.V. Thiel, P. Westra, and A.M. Soeterboek, J. Chromatogr. B 275, 345 (1983).
• [7] J. Tencheva, I. Yamboliev, and J. Zhivkova, J. Chromatogr., B, 421, 396 (1987).
• [8] G. S. J. Mannens, C.A.W. Snel, J. Hendrickx, T. Verhaeghe, L.L. Jeune, W. Bode, L.V. Beijsterveldt, K. Lavrijsen, J. Leempoels, N.V. Osselaer, A.V. Peer, and W. Meuldermans, Drug Metab. Disp., 30, 553 (2002).
• [9] J. Monbaliu, T. Verhaeghe, B. Williems, W. Bode, and K. Lavrijsen, Arzneim. Forsch. Drug Res., 53, 486 (2003).
• [10] T. Verhaeghe, L. Diels, R. de Vries, M. De Meulder, and J. de Jong, J. Chromatogr., B, 789, 337 (2003).
• [11] W.C. Paul, J. Scatina, and F. Samuel, Sisenwine, 18, 1801 (1995).
• [12] R.V.S. Nirogi, V. N. Kandikere, K. Mudigonda, and S. Maurya, J. Chromatogr. Sci., 45, 97 (2007).
• [13] V. Ravinder, S. Ashok, A.V.S.S. Prasad, G. Balaswamy, Y.R. Kumar, and B. Vijaya Bhaskar, Chromatography, 67, 331 (2008).
• [14] United States Pharmacopeia, 34, vol.2, 2011, 2945–2948.
• [15] European Pharmacopoeia, 7th edn., 2010, vol. 2, 2083–2086.
• [16] L.A. Marques, I. Maada, F.J.J. Kanterb, H. Lingemana, H. Irth, W.M.A. Niessen, and M. Gieraa, J. Pharm. Biomed. Anal. 55, 85 (2011).
• [17] C.M. Halpin, C. Reilly, and J.J. Walsh, J. Chem. Ed., 87, 1242 (2010).
• [18] V. Dora, J. Ilias, V. A. Willy, V. Tom, R. Dirk, and D.S. Maurits, Electrophoresis, 26, 1541 (2005).
• [19] ICH Guideline, Q1A (R2) Stability Testing of New Drug Substances and Products, step 4, February 6, 2003.
• [20] J. Malakova, M. Nobilis, Z. Svoboda, M. Lisa, M. Holcapek, J. Kvetina, J. Klimes, and Vladimir J. Chromatogr., B, 853, 265 (2007).