Determination of ionization constants for sequinidazole in aqueous solutions and mixtures of water with isopropanol, acetonitrile and ethanol

Abstract

Seknidazole is a drug from the 5-nitroimidazole group with a number of side-effects. This drug is virtually unexplored from the point of view of chemico-toxicological analysis (CTA). Therefore, the development of a set of methods for the detection and quantification of secnidazole in biological fluids for use in CTA is an urgent task. Aim. To study the acid-base equilibrium of secnidazole in aqueous solutions and mixtures of water with amphiphilic solvents and determine the corresponding ionization constants. Materials and methods. Spectrophotometric measurements were performed using a SPEKOL®1500 single-beam spectrophotometer. An EV-74 ionomer was used to control the pH of the solutions. Seknidazole solutions in the concentrationof 1000 μg/ml were used in the experiment. Results and discussion.  Absorption spectra of secnidazole in water and mixtures of water and amphiphilic solvents in the pH range studied showed four isobestic points characterizing two protolytic equilibria (equilibrium 1 – 240 and 295 nm, equilibrium 2 – 261 and 297 nm). The position of the isobestic points of equilibrium 2 fluctuated in the range ± 3 nm; it was due to the presence of tautomeric transformations for the molecular form of secnidazole. Conclusions. The acid-base equilibria of secnidazole in aqueous solutions and mixtures of water with amphiphilic solvents have been studied. It has been shown that in a strongly alkaline medium there is an anionic form of secnidazole R–, with further decrease in the pH value the molecular form HR appears, in a strongly acidic medium the final product – a protonated form H2R+ – is formed. The ionization constant 1 has been determined for aqueous solutions of secnidazole, mixtures of water with isopropanol, acetonitrile and ethanol. It is impossible to determine the equilibrium constant 2 by the method specified.