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The protolytic equilibria of 13 4-aryl-2,4-dioxobutanoic acids (ADKs) were spectrophotometrically studied in aqueous solutions in the pH range 1-9 at 25±1 °C and an ionic strength of 0.1 mol l-1 (NaCl), with the exception of the 4-OH-derivative which was also potentiometrically studied in the pH range 7-10 at 25±1 °C and an ionic strength of 0.1 mol l-1 (NaCl). In solution, the compounds simultaneously exist in one diketo and two enolic forms; therefore, the determined acidity constants (pKa1 1.87-2.29, pKa2 6.63-8.13 and pKa3(4-OH-) 9.52) represent system macro constants. The 1H-NMR spectrum of the parent compound (4-phenyl- -2,4-dioxobutanoic acid) (25 °C, pD 5.0) proved the existence of all tautomeric forms. Using the extended Hammett relation, the determined pKa values were correlated with literature σ values. The predicted pKa values were in fair accordance with the experimentally observed ones. Molecular, monoanionic and dianionic forms of the parent compound were optimized by the semi-empirical molecular orbital PM6 method using the implicit water solvation model (COSMO). The obtained geometries were used to explain the quality of the LFER models.

The acid-base equilibria of a novel hepatobiliary imaging agent, 2,4-diiodo-6-methylphenylcarbamoylmethyl iminodiacetic acid (DIIODIDA) were studied. The potentiometrically determined acidity constants of the second carboxylic group, amino and amide groups were pK2 = 2.52 ± 0.02; pK3 = 5.86 ± 0.06 and pK4 = 10.9 ± 0.1. The determinations were performed at 25 ºC and an ionic strength of 0.1 mol/dm3 (NaCl). The acidity constants (pK1 = 1.3 ± 0.4) corresponding to the first carboxylic group was determined indirectly, on the basis of equilibrium constants obtained in a heterogeneous system, at 25 ºC and an ionic strength 1 mol/dm3 (HCl, NaCl). DIIODIDA was labeled with technetium-99m, and the influence of pH on the yield of labeling was investigated. It was found that labeling within the pH range from 5.5 to 6.5 provided a radiopharmaceutical of high radiochemical purity (>98 %).

The acid-base equilibria of a diprotic, slightly hydrosoluble base ketoconazole were studied in homogeneous and heterogeneous water systems. The determinations were performed at 25ºC at a constant ionic strength of M(NaCl). The acidity constant Ka1 was determined by potentiometric (pKa1 3.20) and spectrophotometric (pKa1 3.26) methods. A pKa2 constant of 6.10 was obtained based on the equilibrium constants pKs0 4.84 and pKs1 -1.26, determined in a heterogeneous ketoconazole system. The obtained values of the constants served to calculate the solubility and the distribution of the equilibrium forms of ketoconazole as a function of pH. On the basis of the distribution of the equilibrium forms of ketoconazole, a spectrophotometric method for the determination of its content in commercial tablets was developed. The determinations were performed at 225 nm in 0.1 M HCl. The method is simple and rapid and enables the direct spectrophotometric determination of the content of ketoconazole without previous isolation.

The equlibria of bifonazole in saturated water solution within the pH range 4 to 10 [I = 0.1 mol/dm3 (NaCl); 25 ºC] were studied spectrophotometrically. Based on the equlibrium constants determined in a heterogeneous system, the acidity constant (pKa = 5.72) and solubility in water (S=10-5.79+10-(pH + 0.07))were calculated. The influence of β-cyclodextrin on bifonazole solubility was examined in the presence of 10-3 and 10-4 mol/dm3 β-cyclodextrin. At pH values over 8, bifonazole solubility was two- and 13-fold increased in the presence of 10-4 and 10-3 mol/dm3 β-cyclodextrin respectively, compared to its solubility in water. The ratio of bifonazole solubility in the presence of β-cyclodextrin and that in water decreased in parallel to the increase of acidity.

The protolytic equilibria of bromazepam, an ampholyte sparingly soluble in water, in homogeneous and heterogeneous systems were studied in the pH range 0–14 at 25ºC and at ionic strength of 0.1 mol/dm3 (NaCl). On the basis of 13C-NMR spectra, the protonation site was predicted – in acidic media the pyridine nitrogen of bormazepam is protonated. The acidity constants of bromazepam were determined spectrophotometrically (pKa1 2.83 and pKa2 11.60) and potentiometrically (pKa1 2.99). In the heterogeneous system the following equilibrium constants were determined: Ks0 =[HA](pKs0 3.44), Ks1 =[H2A+]/[H3O+](pKs1 0.61), and Ks2 =[A-][H3O+](pKs2 15.04).

1. Introduction 2. Basic characteristics of derivative spectrophotometry 2.1. Increase of spectra resolution 2.2. Elimination of the influence of baseline shift and matrix interferences 2.3. Enhancement of the detectability of minor spectral features 2.4. Precise determination of the positions of absorption maxima 2.5. Signal-to-noise ratio (SNR) 2.6. Quantitative analysis 3. Analytical applications 3.1. Inorganic analysis 3.2. Organic and pharmaceutical analysis 3.3. Analysis of food and water 3.4. Application of derivative spectrophotometry for the determination of equilibrium constants