Open AccessHydrolytic Degradation Study of Rivaroxaban: Degradant Products Identification by LC-MS Isolation by Prep-HPLC and Characterization by HRMS, NMR and FT-IR
Author(s) -
G. Madhusudhan Reddy,
Raghu Babu Korupolu,
B. Babu,
J.C.M.K.N.N. Murty Singamsetti,
Chidananda Swamy Rumalla,
Muralidharan Kaliyaperumal,
Raju Doddipalla,
Rajani V ijay
Publication year - 2020
Publication title -
asian journal of chemistry/asian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.145
H-Index - 34
eISSN - 0975-427X
pISSN - 0970-7077
DOI - 10.14233/ajchem.2020.22888
Subject(s) - chemistry , hydrolysis , high performance liquid chromatography , acetic acid , chromatography , degradation (telecommunications) , mass spectrometry , nuclear chemistry , organic chemistry , telecommunications , computer science
Present work illustrates the stress degradation behaviour of rivaroxaban under hydrolytic, oxidative,thermal and photolytic conditions as per ICH guidelines. Under thermal and photolytic conditionsdrug had a fair stability where as in other stress conditions degradation products were observed. Initialidentification of the degradation products was performed by hyphenated mass spectrometry coupledto ultra-performance liquid chromatography (UPLC-MS) and mass directed auto purification (MDAP)was used for isolation. Various 1D and 2D nuclear magnetic resonance (NMR) were performed tocharacterize the degradation products which were assisted by FT-IR and HRMS data. Two noveldegradant products were observed in hydrolytic conditions, isolated and characterized by spectroscopictechniques as (R)-2-(2-((4-((3-(5-chlorothiophene-2-carboxamido)-2-hydroxypropyl)amino)phenyl)-amino)ethoxy)acetic acid (DP-2) (m.w. of 427.90 g/mol and m.f. C18H22N3O5SCl), and5-chlorothiophene-2-carboxylic acid (DP-3) (m.w. 161.95 g/mol and m.f. C5H3O2SCl). Additionally,two more degradation products were observed in basic and acidic conditions, viz. (R)-5-chloro-N-(2-hydroxy-3-((4-(3-oxomorpholino)-phenyl)amino)propyl)thiophene-2-carboxamide (DP-1) (m.w.409.09 g/mol and m.f. C18H20N3O4SCl) and (S)-2-(2-((4-(5-((5-chlorothio-phene-2-carboxamido)methyl)-2-oxooxazolidin-3-yl)phenyl)amino)ethoxy)acetic acid (DP-4) (m.w. 453.08g/mol and m.f. C19H20N3O6SCl) are already reported.