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The acid-base equilibria of a diprotic, slightly hydrosoluble base ketoconazole were studied in homogeneous and heterogeneous water systems. The determinations were performed at 25 degreesC at a constant ionic strength of 0.1 M (NaCl). The acidity constant K,,, was determined by potentiometric (pK(a1) 3.20) and spectrophotometric (pK(al) 3.26) methods. A pK(a2) constant of 6.10 was obtained based on the equilibrium constants pK(s0) 4.84 and pK(s1) -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., Proučene su kiselinsko-bazne ravnoteže u homogenom i heterogenom vodenom sistemu ketokonazola, diprotične teško rastvorne baze. Određivanja su vršena na temperaturi 25ºC i pri konstantnoj jonskoj sili 0,1M(NaCl). Kiselinska konstantaKa1 određena je potenciometrijski (pKa1 3,20) i spektrofotometrijski (pKa1 3,26). Konstanta pKa2 6,10 izračunata je iz ravnotežnih konstanti određenih u heterogenom sistemu: pKs0 4,84 i pKs1 -1,26. Na osnovu dobijenih vrednosti za konstante izračunata je rastvorljivost i raspodela ravnotežnih oblika ketokonazola u funkciji pH. Na bazi raspodele ravnotežnih oblika ketokonazola predložena je spektrofotometrijska metoda za njegovo određivanje u komercijalnim tabletama. Određivanja su vršena na talasnoj dužini 225 nm u 0,1M HCl.Metoda je jednostavna i brza, i omogućava direktno spektrofotometrijsko određivanje ketokonazola, bez prethodnog izolovanja.

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 25 degreesC and at ionic strength of 0.1 mol/dm(3) (NaCl). On the basis of C-13-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 (pK(a1) 2.83 and pK(a2) 11.60) and potentiometrically (pk(a1) 2.99). In the heterogeneous system the following equilibrium constants were determined: K-s0 = [HA] (pK(s0) 3.44), K-s1 = [H(2)A(+)]/[H3O+] (pK(s1) 0.61), and K-s2 = [A(-)][H3O+] (pK(s2) 15.04)., Proučavane su protolitičke ravnoteže bromazepama, amfolita iz klase 1,4-benzodiazepina, slabo rastvornog u vodi. Ispitivanja su vršena u homogenom i heterogenom sistemu u pH intervalu 0–14, na temperaturi 25ºC i pri jonskoj sili 0,1 mol/dm3 (NaCl). Na osnovu 13C-NMR spektara pretpostavljeno je da do protonovanja u molekulu bromazepama dolazi na piridinskom atomu azota. Kiselinske konstante određene su spektrofotometrijski (pKa1 2.83 and pKa2 11.60) i potenciometrijski (pKa1 2,99). U heterogenom sistemu određene su sledeće ravnotežne konstante Ks0 =[HA](pKs0 3.44), Ks1=[H2A+]/[H3O+](pKs1 0.61), and Ks2 =[A-][H3O+](pKs2 15.04).