title: Characterization of three main degradation products from novel oral anticoagulant rivaroxaban under stress conditions by UPLC-Q-TOF-MS/MS.
abstract: Drugs of long-term use may cause the accumulation of chemical compounds in human body. Therefore, the evaluation and structure characterization of synthesis and degradation impurities is substantial to guarantee drug safety and successful pharmaceutical therapy. The present work evaluated the anticoagulant rivaroxabana (RIV) under stress conditions in order to elucidate the chemical structure of major degradation products (DPs) formed after drug exposition to acid and alkaline hydrolysis, and UVC radiation. Analyses were performed in UPLC coupled to quadrupole time-of-flight MS. ESI was applied in positive mode, and C18 Agilent(®) column (2.1×50 mm, 1.8 μm) used for separation of compounds. RIV molecular íon [M+H](+) (m/z 436.07) was fragmented under 20 kV, best energetic condition to obtain clear and reproducible fragmentation pattern, assisting identification of RIV DPs. With support from UPLC separation and specific detection by MS/MS, three main degradation products (DP-1, DP-2, and DP-3) formed under stress conditions were successfully characterized. Presented study agrees with requirements for analytical assessment of impurities in pharmaceutical formulations, ensuring quality of pharmaceutical substances.
authors: Laboratory of Pharmaceutical Quality Control, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: nath.rw@gmail.com.
authors: Nathalie R
authors: NR
authors: Wingert
authors: Laboratory of Pharmaceutical Quality Control, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Natália O
authors: NO
authors: dos Santos
authors: Chemistry Department, Universidade Federal do Santa Maria, Santa Maria, Brazil.
authors: Matheus A G
authors: MA
authors: Nunes
authors: Graduation Program in Nanosciences, Centro Universitário Franciscano, Santa Maria, Brazil.
authors: Patrícia
authors: P
authors: Gomes
authors: Chemistry Department, Universidade Federal do Santa Maria, Santa Maria, Brazil.
authors: Edson I
authors: EI
authors: Müller
authors: Chemistry Department, Universidade Federal do Santa Maria, Santa Maria, Brazil.
authors: Érico M M
authors: ÉM
authors: Flores
authors: Laboratory of Pharmaceutical Quality Control, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Martin
authors: M
authors: Steppe
mesh_terms: D000143:Acids / Q000737:chemistry; D000925:Anticoagulants / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D004355:Drug Stability; D006868:Hydrolysis; D000069552:Rivaroxaban / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000143:Acids; D000925:Anticoagulants; D000069552:Rivaroxaban
keywords: Chemical characterization; Degradation products; Rivaroxaban; UPLC–MS/MS