Isolation and structural characterization of novel photolytic degradation impurities of Deflazacort using Q-TOF, 2D-NMR and FTIR.

Forced Degradation of Deflazacort drug substance in ultraviolet light condition resulted into a number of significant degradation products. Two of these degradation products were found to be unknown during the study and marked as DD-I and DD-II. Thus, the objective of this work is to investigate and identify these two novel degradation products of DFZ. The isolation method for these new degradation products were developed using a new reverse-phase high performance liquid chromatography (HPLC). DD-I and DD-II, eluting at 0.53 and 1.57 relative retention times with respect to Deflazacort (DFZ) peak respectively, were isolated from reaction mass using preparative HPLC and their structures were elucidated using high resolution MS, multidimensional NMR and FTIR spectroscopic techniques. To best of our knowledge, these two degradation products are novel impurities which are not discussed in any form of publication yet.

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

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.