Victoria Sanz-Nebot

Comparison between capillary electrophoresis, liquid chromatography, potentiometric and spectrophotometric techniques for evaluation of pKa values of zwitterionic drugs in acetonitrile-water mixtures

Abstract Capillary electrophoresis, liquid chromatography, potentiometry and UV–visible spectrophotometry are frequently used for determination of pKa values of substances. In this work, we have compared the application of the different techniques to the determination of pKa values of a series of zwitterionic quinolones in acetonitrile–water mixtures, emphasizing the advantages of capillary electrophoresis for the determination of equilibrium constants of widely used drugs in aqueous and aqueous organic media.

Solvatochromic parameter values and pH in aqueous-organic mixtures used in liquid chromatography. Prediction of retention of a series of quinolones

Abstract The proportion of the organic modifier and the pH of the mobile phase were optimized in order to separate six important quinolones: ciprofloxacin, norfloxacin, enoxacin, fleroxacin, ofloxacin and pipemidic acid. The mobile phase was optimized by establishing relationships between retention parameters and the Reichardts E T N scale of solvent polarity, and between retention and the Kamlet-Taft multiparameter solvent scale of the eluent, using linear solvation energy relationships (LSER). In addition, the effect of liquid junction potentials was studied in cells with commercial potentiometric sensors in order to determine the highest precision and accuracy in pH measurements achievable in acetonitrile-water mixtures used as mobile phases. This pH allows the optimization of the mobile phase pH for the chromatographic separation required.

Preferential solvation in acetonitrile–water mixtures. Relationship between solvatochromic parameters and standard pH values

Standard pH values; pH(s), for five reference buffer solutions, KH tartrate, KH2 citrate, KH phthalate, acetate buffer and phosphate buffer in acetonitrile–water mixtures containing 10, 30, 40, 50, 70 and 100 wt. % acetonitrile at 298.15 K have been determined using the IUPAC standardization rules. The relationship between pH(s) and solvent composition, expressed as a fraction, have been studied, with a view to assessing the presence of preferential solvation effects. In order to obtain pH(s) values for all possible acetonitrile–water mixtures, the linear solvation energy relationships method, LSER, has been applied. The pH(s) values were then correlated with the Kamlet–Taft, π*, α and β solvatochromic parameters of the acetonitrile–water mixtures. The equation obtained permits the standardization of potentiometric sensors in these mixtures.

Retention behaviour of quinolone derivatives in high-performance liquid chromatography. Effect of pH and evaluation of ionization constants.

This paper examines the effect of solute ionisation on the retention behaviour of a series of quinolones and evaluates their pKa values using chromatographic data in acetonitrile-water mixtures with acetonitrile percentages of 30, 35, 40 and 50% (v/v). We also compare these pKa values with those previously obtained in acetonitrile-water mixtures from potentiometric measurements. In doing so, the pH values were measured in the hydroorganic mixture, which was used as the mobile phase, instead of in water, taking into account the effect of activity coefficients. The resulting equations permit the chromatographic determination of the pKa values of the quinolones in acetonitrile-water mixtures and also permit the prediction of the effect of pH on their chromatographic behaviour. These equations can be combined with those previously derived, which relate retention to the solvent composition of the mobile phase, to establish a general model that relates the elution behaviour of the solute to significant mobile phase properties: composition, pH and ionic strength.

Ionization constants of pH reference materials in acetonitrile—water mixtures up to 70% (w/w)

Abstract Ionization constants of pH reference materials in acetonitrile—water mixtures containing 30, 40, 50 and 70% (w/w) acetonitrile were obtained. The ionization constant values determined were: p K 1 and p K 2 for tartaric and phthalic acid; p K 1 , p K 2 and p K 3 for citric acid and p K 1 for fabric and acetic acid. These values are essential to determine the standard reference value, pHs, for various standard reference buffer solutions. In the total composition range studied, p K values were linearly correlated with the mol fraction of acetonitrile and with the reciprocal of the dielectric constant of solvent mixtures. Considering the unlimited number of solvent mixtures, a multilinear regression procedure was applied to correlate p K values with % (w/w) and % (v/v) of acetonitrile, and the methodology of linear solvation energy relationships (LSERs) was used to relate p K data with solvatochromic parameters of acetonitrile—water mixtures.

Protonation equilibria of quinolone antibacterials in acetonitrile-water mobile phases used in LC

Ionization constants of nine quinolone antibacterials in acetonitrile-water mixtures containing 0, 5.5, 10, 16.3, 25, 30, 40, 50 and 70% (w/w) acetonitrile were obtained and assignment of these pK values to the several potentially ionizable functional groups was made. The variation of the pK values obtained over the whole composition range studied can be explained by consideration of the preferential solvation of electrolytes in acetonitrile-water mixtures. In order to obtain pK values in any of the unlimited number of possible binary solvent acetonitrile-water mixtures, relationships between pK values and different bulk properties (such as dielectric constant) were examined. The linear solvation energy relationships method, LSER, was applied to study the correlation of pK values with the solvatochromic parameters of acetonitrile-water mixtures. The equations obtained allow calculation of the pK values of the quinolone antimicrobials in any acetonitrile-water mixtures up to 70% (w/w) and thus permit the knowledge of the acid-base behaviour of these important antimicrobials in the widely used acetonitrile-water media.

Modelling retention in liquid chromatography as a function of solvent composition and pH of the mobile phase.

The aim of this work was to develop a model that accurately describes retention in liquid chromatography (LC) as a function of pH and solvent composition throughout a large parameter space. The variation of retention as a function of the solvent composition, keeping other factors constants, has been extensively studied. The linear relationship established between retention factors of solutes and the polarity parameter of the mobile phase, E(N)T, has proved to predict accurately retention in LC as a function of the organic solvent content. Moreover, correlation between retention and the mobile phase pH, measured in the hydroorganic mixture, can be established allowing prediction of the chromatographic behavior as a function of the eluent pH. The combination of these relationships could be useful for modelling retention in LC as a function of solvent composition and pH. For that purpose, the retention behavior on an octadecyl silica column of a group of diuretic compounds covering a wide range of physico-chemical properties were studied using acetonitrile as organic modifier. The suggested model accurately describes retention of ionizable solutes as concomitant effects of variables included and is applicable to all solutes studied. We also aimed to establish an experimental design that allows to reproduce to a good approximation the real retention surface from a limited number of experiments, that is from a limited number of chromatograms. Ultimately, our intention is to use the model and experimental design for the simultaneous interpretive optimization of pH and proportion of organic solvent of the mobile phase to be used in the proposed separation.

Solvatochromic parameter values and pH in acetonitrile-water mixtures optimization of mobile phase for the separation of peptides by high-performance liquid chromatography☆

The proportion of the organic modifier and the pH of the mobile phase were optimized in order to separate a series of low-molecular-mass peptides by HPLC. The composition of the mobile phase was optimized by establishing relationships between retention parameters and Reichardts ENT scale of solvent polarity, and between retention and the Kamlet-Taft multiparameter solvent scale of the eluent, using linear solvation energy relationships (LSER). The pH of the mobile phase was also successfully optimized by establishing relationships between the retention and the pH measured in the aqueous-organic mixture used as eluent.

The application of factor analysis to solvatochromic parameters and pHs values for the standardization of potentiometric sensors in mobile phases used in liquid chromatography

Abstract The pH s values for reference buffer solutions in aqueous acetonitrile, methanol, and tetrahydrofuran mixtures used as mobile phases in LC were subjected to factor analysis in order to discover the number of factors which affect the variation with the percentage of organic co-solvent of the whole data sets. Afterwards, target factor analysis was used to identify these factors. The pH s values were correlated with the solvatochromic parameters (π*, α, β, and E T ) of the hydro-organic mixtures according to the results obtained using these chemometric techniques. An equation is proposed which permits the calculation of pH s values in any aqueous acetonitrile, methanol, or tetrahydrofuran mixtures, and thus accurate pH measurements can be made in these media as well as in water. An overview of the effects on pH s values of preferential solvation in these media is also presented.

AUTOPROTOLYSIS CONSTANTS AND STANDARDIZATION OF THE GLASS ELECTRODE IN ACETONITRILE-WATER MIXTURES. EFFECT OF SOLVENT COMPOSITION

Abstract Standard e.m.f.s for the cell GE/HCl/AgCl/Ag/Pt (GE=glass electrode) in acetonitrile-water mixtures containing 0–70% (w/w) of acetonitrile were obtained. Values of the autoprotolysis constant, Kap, of these mixed solvents were also determined from e.m.f. measurements of the cell GE/KCl + KS/AgCl/Ag/Pt. The influence of variations in the solvent composition on pKap values was evaluated. Over the whole of the composition range studied the pKap values were linearly correlated with the mole fraction of acetonitrile and with the reciprocal of the relative permittivity of solvent mixtures. Linear relationships were also obtained for pKap values vs. the Kamlet-Taft π★ polarizability/dipolarity parameter in the range 0–50% (w/w).