Isolation and characterization of novel degradation products of Doxofylline using HPLC, FTIR, LCMS and NMR.

Forced degradation of Doxofylline (DFL) in different stress (base and peroxide) conditions gave rise to two potential unknown impurities. These unknown degradation products DFL DEG-I and DFL DEG-II were evaluated using a new-reverse-phase high performance liquid chromatography (HPLC), where it was eluted at 0.44 and 1.09 relative retention times to DFL peak. DFL DEG-I and DFL DEG-II were isolated using preparative HPLC from degradation mixtures. The structure of DFL DEG-I and DFL DEG-II were elucidated using high resolution MS, multi-dimensional NMR and FTIR spectroscopic techniques, and characterized. The stereochemistry of the enantiomers in DFL DEG-II has further been investigated using computational techniques. To the best of our knowledge, DFL DEG-I and DFL DEG-II are novel impurities and not reported elsewhere.

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.

The novel acid degradation products of losartan: Isolation and characterization using Q-TOF, 2D-NMR and FTIR.

Forced degradation of losartan potassium in acidic condition resulted into three potential unknown impurities. These unknown degradation products marked as LD-I, LD-II and LD-III were analyzed using a new reverse-phase high performance liquid chromatography (HPLC), eluting at 3.63, 3.73 and 3.91 relative retention times with respect to losartan potassium (LOS) peak. All three were isolated from reaction mass using preparative HPLC and their structures were elucidated using LC-MS/MS, multidimensional NMR and FTIR spectroscopic techniques, as 5(2),11(2)-dibutyl-5(4),11(4)-dichloro-1(1)H,5(1)H,7(1)H,11(1)H-1(5,1),7(1,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane,(Z)-5(2),11(2)-dibutyl-5(4),11(4)-dichloro-1(1)H,5(1)H,7(2)H,11(1)H-1(5,1),7(2,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane, and 5(2),11(2)-dibutyl-5(4),11(4)-dichloro-1(2)H,5(1)H,7(2)H,11(1)H-1(5,2),7(2,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane, respectively. To best of our knowledge, all three degradation products are novel impurities which are not discussed at 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.

Isolation and characterization of a novel acid degradation impurity of Amlodipine Besylate using Q-TOF, NMR, IR and single crystal X-ray.

Forced degradation of Amlodipine Besylate (AMD) in acidic condition gave rise to a potential unknown impurity. This unknown acid degradation product (ADP) was evaluated using a new-reverse-phase high performance liquid chromatography (HPLC), where it was eluted at 1.24 relative retention time to AMD peak. ADP was isolated using preparative HPLC from degradation mixture. Later, structure of ADP was elucidated using high resolution MS, multidimensional NMR and FTIR spectroscopic techniques, and characterized as ethyl-6-(2-chlorophenyl)-8-methyl-3,4,6,7-tetrahydro-2H-benzo[b][1,4]oxazine-5-carboxylate. The presence of ADP recemic mixture was confirmed by polarimeter and chiral HPLC. Given the complexity associated with ADP generation, single crystal X-ray crystallography technique was used to confirm proposed structure. In addition, reaction mechanism was postulated and confirmed using computational chemistry. To our knowledge, it is a novel impurity and not reported elsewhere.