Protolitičke ravnoteže u homogenom i heterogenom sistemu ketokonazola i njegovo direktno spektrofotometrijsko određivanje u tabletama

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.