Multi-wavelength spectrophotometric determination of propofol acidity constant in different acetonitrile-water mixtures

Abstract

A constante ácido-base de uma droga anestésica, propofol, foi determinada em diferentes misturas acetonitrila-água usando-se dados de titulação espectrofotométrica multivariada. Os valores de pH medidos com eletrodo de vidro calibrado com tampão aquoso, nas misturas acetonitrila-água, s w pH, foram corrigidos para obter-se o s s pH, que é o pH da mistura acetronitrila-água medido com eletrodo de vidro, calibrado com tampão na mesma mistura de solvente. Essa escala de pH está diretamente relacionada com a constante termodinâmica ácido-base. O valor de pK a do propofol encontrado em água é de 11,67. Relações lineares foram observadas quando os valores calculados de pK a do propofol, em diferentes misturas de solvente, foram comparados com a fração molar de acetonitrila. Uma relação linear foi também encontrada entre os valores de pK a e a permissividade relativa recíproca da mistura de solventes, 1/ε. Este comportamento foi considerado como indicativo da natureza eletrostática do processo de ionização.The acid-base constant of an anaesthetic drug, propofol, was determined in different acetonitrilewater mixtures by using multiwavelength spectrophotometric titration data. The pH values measured in acetonitrile-water mixtures with a glass electrode calibrated with an aqueous buffer, s w pH, were corrected to obtain s s pH, that is, the pH of the acetonitrile-water mixture as measured with a glass electrode calibrated with a buffer in the same solvent mixture. This last pH scale is directly related to the thermodynamic acid-base constant. The pK a value of propofol in pure water was found to be 11.67. Linear relationships were observed when the calculated pK a values of propofol in different solvent mixtures were plotted against the acetonitrile molar fraction. Also, a linear relationship was observed between pK a values and the reciprocal of the relative permittivity of the solvent mixture, 1/ε. This behavior was taken as indicative of the electrostatic nature of the ionization process.

Lipophilicity of some GABAergic phenols and related compounds determined by HPLC and partition coefficients in different systems

“…In the dissociation of neutral or anion acids, charges are created and the dissociation process is disturbed when the relative permittivity of the medium decreases with the increase in ACN content (relative permittivity of ACN and water: 38.8 at 20 • C and 78.5 at 25 • C, respectively). Hence, for the dissociation of phenolic protons, the electrostatic interaction exceeds the specific solvation and the pKa increases with the percentage of ACN in the mixture (see Pissinis et al [35] and references therein). According to this, it would be expected that the presence of ACN in our experiments would increase the phenolic pKa values even more, highlighting the fact that, under the present experimental conditions, there is neither ionization of any compounds nor charge effects.…”

Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine

“…The highest recovery yield of propofol was obtained at pH 8 where propofol ionization in aqueous solution is the lowest [24]. However, sufficient recovery of hydroxylated metabolites was obtained at pH 6.5-7.0 because these compounds had lower pK a values than propofol.…”

Electrochemical Detection of 2,6‐Diisopropylphenol (Propofol) in Reversed Phase HPLC at High pH

“…The pK a value for propofol in 90:10 (v/v) buffer-ACN mixtures is approximately 11.93. [13] Thus, propofol is mainly present as an anion at pH 13.8, the phenolate derived ion. It is known that phenolate ions are oxidized at lower electrode potentials as compared to the neutral species.…”

“…Propofol is a weakly acidic compound (pK a ¼ 11.65), [13] which can be ionized at high pH. Retention of acidic, as well as basic, solutes in reversed phase chromatographic columns is strongly influenced by the pH of the mobile phase, [14,15] ionized compounds eluting earlier than unionized ones.…”