Determination of pK_a values by capillary zone electrophoresis with a dynamic coating procedure

Abstract

CZE allows to measure the acidic dissociation constant (pKa) of many drug substances. However, determining the EOF intensity may be time-consuming, especially at a low pH. In order to overcome this drawback, a dynamic coating procedure of the capillary was carried out to increase microEOF, and thus to reduce the analysis time. In addition, this coating procedure enhanced migration time stability. The effective mobilities of 15 compounds were measured at different pH, producing pK'a values dependent on BGE ionic strength. The latter values were corrected with the activity coefficient to obtain a "true" pKa value. The 15 investigated compounds were (i) five acids: namely, salicylic acid, benzoic acid, ketoprofen, phenobarbital, and phenol, (ii) four bases: lidocaine, propafenone, propranolol, and quinine, (iii), five ampholytes: sulfanilamide, sulfabenzamide, sulfadimethoxine, sulfadoxine, and sulfisoxazole, and (iv) one zwitterion: cetirizine. The range of determined pKa values was between 1.2 and 11.2, and close to the pKa values available from the literature.

Recent advances in the analysis of antibiotics by CE and CEC

“…Likewise, the determination of pK a values for several sulfonamide antibiotics by CE was reported [64]. However, the main applications of the developed CE and CEC methodologies were the analysis of antibiotics in a great variety of samples, including pharmaceutical formulations, agrochemical bactericidal products, and biological, food and feed, and environmental samples, as illustrated in Table 7.…”

Determination of Acid Dissociation Constants of Poorly Water-Soluble Nicotinic Ligands by Means of Electrophoretic and Potentiometric Techniques

“…Sample concentrations were very low (0.02 mg/ mL) because all compounds were poorly soluble in water. Twenty- one buffers, set at an ionic strength of 20 mM, were prepared from pH 2.0 to pH 12.0 with an increment of 0.5 pH units according to Geiser et al [19]. The buffers were degassed in an ultrasonic bath prior to use and were replaced every ten runs, thus avoiding electrolytic phenomena.…”

“…A non-linear regression was performed to determine pK' a values which were dependent on the BGE concentration. These values were corrected by introducing an activity coefficient, which gave the "true" pK a value, independent of experimental procedures [19].…”

Determination of Acid Dissociation Constants of Compounds Active at Neuronal Nicotinic Acetylcholine Receptors by Means of Electrophoretic and Potentiometric Techniques

“…Twenty-one buffers spanning the range pH 2.0 -12.0, with an increment of 0.5 pH units, were prepared according to Geiser et al 20 and their ionic strength was set at 20 mM (Table S1, Supporting Information). The buffers were degassed in an ultrasonic bath prior to use and were replaced every ten runs, thus avoiding electrolytic phenomena.…”

“…These values were corrected by introducing an activity coefficient in order to obtain the "true" pKa value independent of the experimental procedures. 20 …”