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Rapolu R.,United States Pharmacopeial Convention India P Ltd. | Raju C.K.,United States Pharmacopeial Convention India P Ltd. | Srinivas K.,United States Pharmacopeial Convention India P Ltd. | Awasthi A.,United States Pharmacopeial Convention India P Ltd. | And 2 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

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-2. H-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. © 2014 Elsevier B.V.


Rapolu R.,United States Pharmacopeial Convention India P Ltd. | Pandey A.K.,United States Pharmacopeial Convention India P Ltd. | Raju C.K.,United States Pharmacopeial Convention India P Ltd. | Ghosh K.,United States Pharmacopeial Convention India P Ltd. | And 4 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2015

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. 1H and 13C 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. © 2015 Elsevier B.V.


Kumar Pandey A.,United States Pharmacopeial Convention India P Ltd. | Rapolu R.,United States Pharmacopeial Convention India P Ltd. | Raju C.K.,United States Pharmacopeial Convention India P Ltd. | Sasalamari G.,United States Pharmacopeial Convention India P Ltd. | And 4 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2016

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 52,112-dibutyl-54,114-dichloro-11H,51H,71H,111H-1(5,1),7(1,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane,(Z)-52,112-dibutyl-54,114-dichloro-11H,51H,72H,111H-1(5,1),7(2,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane, and 52,112-dibutyl-54,114-dichloro-12H,51H,72H,111H-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. © 2015.Published by Elsevier B.V.

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