Determination of p<i>K</i>_a Values for Some Benzimidazole and Imidazole Group Drugs Using the Reversed-Phase Liquid Chromatography Method

Abstract

The benzimidazole and imidazole rings are the most important heterocyclic structures that show a promising application in the pharmaceutical industry. Many potent marketed drugs containing imidazole or benzimidazole rings have different biological activities such as anthelmintic, antifungal, antiviral, and anticancer. In the present study, thermodynamic dissociation constant (pKa) values for some benzimidazole- and imidazole-containing drugs (albendazole, astemizole, clotrimazole, metronidazole, thiabendazole, and thiamazole) in acetonitrile + water binary mixtures except for thiamazole were determined by reversed-phase liquid chromatography (RPLC) method at 25 °C. The aqueous pKa values of the hydrophobic drugs were calculated using certain selected macroscopic parameters. The resultant aqueous pKa values were 5.499 for clotrimazole, 3.039 for metronidazole, 10.858 for thiamazole, 3.799 for albendazole, 4.593 for thiabendazole, and 6.214 and 8.910 for astemizole. Linear solvation energy relationships (LSERs) based on the Abraham solvation parameter model have been successfully used to predict the biorelevant pKa values (37 °C) of the studied drugs.