A novel UV degradation product of Ebastine: isolation and characterization using Q-TOF, NMR, IR and computational chemistry.

Ravi Rapolu, Avadhesh Kumar Pandey, Ch Krishnam Raju, Kaushik Ghosh, Kolupula Srinivas, Atul Awasthi, Sameer G Navalgund, Koduru V Surendranath

Index: J. Pharm. Biomed. Anal. 107 , 488-94, (2015)

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Abstract

Forced degradation of Ebastine (1-(4-(1,1-dimethylethyl)phenyl)-4-(4-(diphenylmethoxy) piperidin-1-yl)butan-1-one) drug substance in ultraviolet light condition resulted into an unknown significant degradation product. This degradation product was analyzed using a newly developed reverse-phase HPLC, where it was eluted at 2.73 relative retention time to Ebastine peak. UV degradation product was isolated from reaction mass using preparative HPLC and its structure was elucidated using high resolution MS, multidimensional NMR and FTIR spectroscopic techniques. UV degradation product has been characterized as 2-(4-(benzhydryloxy)piperidin-1-yl)-1-(4-(tert-butyl)phenyl)-2-methylcyclopropanol. (1)H and (13)C NMR chemical shift values were generated using computational chemistry for possible two diastereomers (7R10S and 7R10R) and later 7R10R was confirmed (and its enantiomer) as final structure given it showed close agreement with experimental NMR data. Formation of UV degradation product as a recemic mixture was further verified by computational chemistry evaluation, chiral HPLC and polarimetery. To best of our knowledge, this is a novel degradation product which is not discussed at any form of publication yet. Copyright © 2015 Elsevier B.V. All rights reserved.