No abstract

The first-order degradation kinetics of epidoxorubicin were investigated as a function of pH, temperature, and buffers concentrations. The degradation was followed by HPLC. Buffer catalysis was observed in acetate and phosphate buffers. The pH-rate profiles were obtained at 333, 343, 353, and 363 K. The pH-rate expression was pHwhere 1 , 4 , and 5 are the second-order rate constants (mol −1 L s −1 ) for hydrogen ion activity and for hydroxyl ion activity, respectively, and 2 and 3 are the first-order constants (s −1 ) for spontaneous reaction under the influence of water. Epidoxorubicin demonstrates the greatest stability in the pH range 3-5. The electrostatic molecular potential orbitals HOMO-LUMO were also defined in order to determine the cause of the reactivity of particular epidoxorubicin molecule domains in solutions with various pH values.

The 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-6-(4-methoxyphenyl)-9-oxo-5H-imidazo[1,2-a]–purine (6-(4-MeOPh)-TACV) was selected to assess the enzymatic stability of the tricyclic acyclovir derivatives from the imidazo[1,2-a]-purine group. The parent compound and its esters (acetyl, isobutyryl, pivaloyl, nicotinic, ethoxycarbonyl) were subjected to kinetic studies and compared with the stability of analogous acyclovir (ACV) esters. The enzymatic hydrolysis was observed in vitro in a medium of 80% human plasma in the absence and presence of porcine liver esterase (PLE). The tests were carried out at 37 °C. To determine the kinetic parameters (kobs., t0.5) of the observed reaction, the validated HPLC-UV method in the reversed phase was used. The HPLC-MS/MS method was used to identify the degradation products under the tested conditions. In summary, it was found that 6-(4-MeOPh)-TACV esters are more susceptible to esterase metabolism than ACV esters. It was confirmed by HPLC-MS/MS that in the plasma, the main product of their hydrolysis is 6-(4-MeOPh)-TACV and not ACV, which confirms that their antiviral activity observed in vitro does not result from ring degradation.

The stress tests as well as photostability analysis in solutions and the solid phase of the oleanoyl oxime ibuprofenate (Ibu‐OxOA) were determined according the International Conference on Harmonization guidelines. For observation of the degradation of tested compounds, the reversed phase high‐performance liquid chromatography (RP‐HPLC) method was used. The study included the effect of temperature, water, H+ and OH− ions, hydrogen peroxide, and light (6.0 × 106, 1.2 × 106 lux·h) on the stability of the tested hybrid. Studies have shown that these compounds are not stable in a neutral, acidic, or oxidizing medium; very unstable in an alkaline medium; and photostable in a solution and photostable in the solid phase. Studies on the enzymatic stability of the tested hybrid showed that it is not susceptible to degradation in the presence of plasma enzymes as well as in the presence of esterase (37°C, 80% human plasma). The degradation of this compound was observed in the presence of lipase (from Candida antarctica), and the linear dependence of the determined kinetic parameters of the reaction on the enzyme activity was demonstrated.

In the presented studies, the effect of hydrogen ions on the stability of the tricyclic aciclovir derivative (i.e. 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-6-(4methoxyphenyl)-9-oxo-5H-imidazo[1,2-a]purine; 6-(4-MeOPh)-TACV) and its esters (acetyl (Ac-), iso-butyryl (iBut-), pivaloyl (Piv-), ethoxycarbonyl (Etc-) and nicotinoyl (Nic-)) has been assessed. The HPLC chromatographic method (Lichrospher RP-18 column, 5 μm, 250 mm × 4 mm) with UV detection (262 nm) was used to observe changes in the concentration of the tested compounds. The mobile phase consisted of acetonitrile-phosphate buffer (pH 6; 20 mM; 17 mM KH 2 PO 4 , 3 mM K 2 HPO 4) (35:65, v/v). The studies were carried out in the pH range 0.42-1.38 in the water-organic environment at constant ionic strength (0.50 M). The observed rate constants of the degradation reactions of the tested compounds were determined, kinetic equations describing the dependence of k pH as a function of pH for the proper acid catalysis were determined and the parameters of the equations describing the reaction of formation the observed product were determined. The dependence of durability on the chemical structure of the tested compounds was indicated and the mechanism of observed reactions was proposed.