0000000000262759
AUTHOR
Ilze Grante
Solvates of Dasatinib: Diversity and Isostructurality
A series of dasatinib crystalline forms were obtained, and a hierarchical cluster analysis of their powder X-ray diffraction patterns was performed. The resulting dendrogram implies 3 structural groups. The crystal structures of several solvates representing 2 of these groups were determined. The crystal structure analysis confirms the isostructurality of solvates within structural group I and suggests a correlation between solvent molecule size and trends in crystal structures within this group. In addition, the formation relationships in 2-solvent media between different dasatinib solvate groups were determined. The formation preference of solvates was found to follow the ranking group I …
The influence of pH on the stability of antazoline: kinetic analysis
Degradation of the drug antazoline was studied in aqueous solutions by means of pH-rate profiling (pH 0–7.4). The novel approach of Runge–Kutta numerical integration in combination with multi-parameter optimisation was applied to UV-Vis spectral data to determine a valid kinetic model and kinetic parameters of the degradation process. The overall degradation mechanism was found to be dependent on the environmental pH. In the pH range of 3.0–7.4, the formation of the antazoline hydrolysis product (N-(2-aminoethyl)-2-(N-benzylanilino)acetamide) through three different pathways (acidic, non-catalysed, and semi-alkaline hydrolysis) was observed. In highly acidic media (pH 0–2), the degradation …
Protonation of Tyrosine Kinase Inhibitor Lapatinib: A Theoretical and Experimental Study
The protonation process of tyrosine kinase inhibitor lapatinib was studied by means of 1HNMR and UV/Vis spectroscopy joint with the theoretical calculations at DFT and semi-empirical levels. DFT/M06-2X geometries were used to describe and compare the different cationic forms of lapatinib, while ZINDO/S-CI method performed on those geometries allowed for the interpretation of experimental UV/Vis spectra of lapatinib at various pH. We found that at low pH two different dicationic forms (N2N1 and N1N3) of lapatinib were present in ethanol and DMSO-d6 solutions. The first protonation, however, occurred on the aliphatic N1 in DMSO-d6, while in ethanol solutions most probably the quinazoline nitr…
Multi-technique approach for qualitative and quantitative characterization of furazidin degradation kinetics under alkaline conditions
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. Complim…
Protonation effects on the UV/Vis absorption spectra of imatinib: A theoretical and experimental study
An experimental and theoretical investigation of protonation effects on the UV/Vis absorption spectra of imatinib showed systematic changes of absorption depending on the pH, and a new absorption band appeared below pH 2. These changes in the UV/Vis absorption spectra were interpreted using quantum chemical calculations. The geometry of various imatinib cations in the gas phase and in ethanol solution was optimized with the DFT/B3LYP method. The resultant geometries were compared to the experimentally determined crystal structures of imatinib salts. The semi-empirical ZINDO-CI method was employed to calculate the absorption lines and electronic transitions. Our study suggests that the forma…
CCDC 910846: Experimental Crystal Structure Determination
Related Article: Kārlis Bērziņš, Artis Kons, Ilze Grante, Diana Dzabijeva, Ilva Nakurte, Andris Actiņš|2016|J.Pharm.Biomed.Anal.|129|433|doi:10.1016/j.jpba.2016.07.039
CCDC 910834: Experimental Crystal Structure Determination
Related Article: Kārlis Bērziņš, Artis Kons, Ilze Grante, Diana Dzabijeva, Ilva Nakurte, Andris Actiņš|2016|J.Pharm.Biomed.Anal.|129|433|doi:10.1016/j.jpba.2016.07.039