Protolytic equilibria in homogeneous and heterogeneous systems of ketoconazole and its direct spectrophotometric determination in tablets

摘要

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 ℃ at a constant ionic strength of 0.1 M (NaCl). The acidity constant K_(a1) was determined by potentiometric (pK_(a1) 3.20) and spectrophotometric (pK_(a1) 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.