title: Multi-technique approach for qualitative and quantitative characterization of furazidin degradation kinetics under alkaline conditions.
abstract: Degradation of drug furazidin was studied under different conditions of environmental pH (11-13) and temperature (30-60°C). The novel approach of hybrid hard- and soft-multivariate curve resolution-alternating least squares (HS-MCR-ALS) method was applied to UV-vis spectral data to determine a valid kinetic model and kinetic parameters of the degradation process. The system was found to be comprised of three main species and best characterized by two consecutive first-order reactions. Furazidin degradation rate was found to be highly dependent on the applied environmental conditions, showing more prominent differences between both degradation steps towards higher pH and temperature. Complimentary qualitative analysis of the degradation process was carried out using HPLC-DAD-TOF-MS. Based on the obtained chromatographic and mass spectrometric results, as well as additional computational analysis of the species (theoretical UV-vis spectra calculations utilizing TD-DFT methodology), the operating degradation mechanism was proposed to include formation of a 5-hydroxyfuran derivative, followed by complete hydrolysis of furazidin hydantoin ring.
authors.affiliation: Faculty of Chemistry, University of Latvia, Jelgavas iela 1, Riga LV-1004, Latvia; Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 308 Harvard Street S.E., Minneapolis, MN 55455, United States. Electronic address: karlis_berzins@live.com.
authors.forename: Kārlis
authors.initials: K
authors.lastname: Bērziņš
authors.affiliation: Faculty of Chemistry, University of Latvia, Jelgavas iela 1, Riga LV-1004, Latvia.
authors.forename: Artis
authors.initials: A
authors.lastname: Kons
authors.affiliation: Faculty of Chemistry, University of Latvia, Jelgavas iela 1, Riga LV-1004, Latvia.
authors.forename: Ilze
authors.initials: I
authors.lastname: Grante
authors.affiliation: Faculty of Chemistry, University of Latvia, Jelgavas iela 1, Riga LV-1004, Latvia.
authors.forename: Diana
authors.initials: D
authors.lastname: Dzabijeva
authors.affiliation: Faculty of Chemistry, University of Latvia, Jelgavas iela 1, Riga LV-1004, Latvia.
authors.forename: Ilva
authors.initials: I
authors.lastname: Nakurte
authors.affiliation: Faculty of Chemistry, University of Latvia, Jelgavas iela 1, Riga LV-1004, Latvia.
authors.forename: Andris
authors.initials: A
authors.lastname: Actiņš
mesh_terms: D005661:Furagin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013696:Temperature
chemical_list: D005661:Furagin
keywords: Computational analysis; Degradation; Furazidin; HPLC-DAD-TOF-MS; HS-MCR-ALS; Kinetic analysis; TD-DFT; UV–vis