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Vol. 32 No. 12 (2020): Vol 32 Issue 12, 2020

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Hydrolytic Degradation Study of Rivaroxaban: Degradant Products Identification by LC-MS Isolation by Prep-HPLC and Characterization by HRMS, NMR and FT-IR

https://doi.org/10.14233/ajchem.2020.22888
G. Mahesh Kumar Reddy
Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., IDA Nacharam, Hyderabad-500076, India ; Department of Engineering Chemistry, Andhra University, Visakhapatnam-530003, India
Raghu Babu Korupolu
Department of Engineering Chemistry, Andhra University, Visakhapatnam-530003, India
B. Kishore Babu
Department of Engineering Chemistry, Andhra University, Visakhapatnam-530003, India
J.C.M.K.N.N. Murty Singamsetti
Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., IDA Nacharam, Hyderabad-500076, India
Chidananda Swamy Rumalla
Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., IDA Nacharam, Hyderabad-500076, India
Muralidharan Kaliyaperumal
Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., IDA Nacharam, Hyderabad-500076, India
Raju Doddipalla
Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., IDA Nacharam, Hyderabad-500076, India
Rajani Vijay
Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd., IDA Nacharam, Hyderabad-500076, India

Corresponding Author(s) : Chidananda Swamy Rumalla

rchidanandaswamy@gmail.com

Asian Journal of Chemistry, Vol. 32 No. 12 (2020): Vol 32 Issue 12, 2020

Abstract

Present work illustrates the stress degradation behaviour of rivaroxaban under hydrolytic, oxidative, thermal and photolytic conditions as per ICH guidelines. Under thermal and photolytic conditions drug had a fair stability where as in other stress conditions degradation products were observed. Initial identification of the degradation products was performed by hyphenated mass spectrometry coupled to 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 to characterize the degradation products which were assisted by FT-IR and HRMS data. Two novel degradant products were observed in hydrolytic conditions, isolated and characterized by spectroscopic techniques 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), and 5-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. 453.08 g/mol and m.f. C19H20N3O6SCl) are already reported.

Keywords

Rivaroxaban Forced Degradation HRMS
Mahesh Kumar Reddy, G., Babu Korupolu, R., Kishore Babu, B., Murty Singamsetti, J., Swamy Rumalla, C., Kaliyaperumal, M., … Vijay, R. (2020). Hydrolytic Degradation Study of Rivaroxaban: Degradant Products Identification by LC-MS Isolation by Prep-HPLC and Characterization by HRMS, NMR and FT-IR. Asian Journal of Chemistry, 32(12), 3035–3042. https://doi.org/10.14233/ajchem.2020.22888
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