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

• Published in: Journal of the Serbian Chemical Society 2005, Vol.70 (1), p.67-78
• Main Authors: Vojic, Mirjana, Popovic, Gordana, Sladic, Dusan, Pfendt, Lidija
• Format: Article
• Language: English
• Subjects: acidity constants; heterogeneous equilibria; ketoconazole; pharmaceuticals; spectrophotometric determination
• ISSN: 0352-5139; 1820-7421
• DOI: 10.2298/JSC0501067V

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?C 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. Proucene su kiselinsko-bazne ravnoteze u homogenom i heterogenom vodenom sistemu ketokonazola, diproticne tesko rastvorne baze. Odredjivanja su vrsena na temperaturi 25?C i pri konstantnoj jonskoj sili 0,1M(NaCl). Kiselinska konstantaKa1 odredjena je potenciometrijski (pKa1 3,20) i spektrofotometrijski (pKa1 3,26). Konstanta pKa2 6,10 izracunata je iz ravnoteznih konstanti odredjenih u heterogenom sistemu: pKs0 4,84 i pKs1 -1,26. Na osnovu dobijenih vrednosti za konstante izracunata je rastvorljivost i raspodela ravnoteznih oblika ketokonazola u funkciji pH. Na bazi raspodele ravnoteznih oblika ketokonazola predlozena je spektrofotometrijska metoda za njegovo odredjivanje u komercijalnim tabletama. Odredjivanja su vrsena na talasnoj duzini 225 nm u 0,1M HCl.Metoda je jednostavna i brza, i omogucava direktno spektrofotometrijsko odredjivanje ketokonazola, bez prethodnog izolovanja.