According to the Bronsted definition, any compound which has a hydrogen atom is an acid, since it may be lost as a proton. A thermodynamical cycle is proposed to calculate absolute pKa values for Bronsted acids in aqueous solution. The equilibrium of dissociation of a Bronsted acid depends on the interaction of the acid and its conjugate base with solvent molecules. There fore the pKa value depends on the solvent medium. The polarizable continuum model (PCM) was used to describe the solvent, and absolute pKa values were computed for different compounds: HCOOH, CH3COOH, C6H5COOH, FCH2COOH and CH3CH2COOH. The model of furnishes pKa values was in good agreement with the experimental results for some classes of compounds. The quantum Mechanics (QM) calculations were carried out with the GAUSSIAN 98 program based on HF/6-31+G** level.

Favipiravir is a broad-spectrum antiviral drug and it has increasing interest regarding its potential use in Covid-19 therapy.  In the present work, a simple, fast, precise Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) technique was developed for the quantification of favipiravir (FVP) from pharmaceutical formulation. Moreover, the spectral and chromatographic behavior of FVP was investigated. The developed method was performed using an ACE 5 C18 column (250 mm × 4.6 mm, 5 µm), with the mobile phase composition 10 mM phosphate buffer (pH = 2.5): methanol (80:20, v/v) at a flow rate 0.6 mL/min. The method validation parameters, such as linearity, precision, accuracy, and robustness, were determined. The recovery yields for accuracy were between 99.9 and 101.4 % for three concentrations. The linearity range was determined between 0.5 and 100 µg/mL with a regression coefficient (R2) 0.99998. The limit of detection and limit of quantification values were evaluated as 0.02 µg/mL and 0.05 µg/mL, respectively. The precision of the method was evaluated in inter-day and intra-day precision studies with a relative standard deviation of less than 2%. The method's robustness was investigated using the alteration of flow rate, detection wavelength, and mobile phase ratio.  Moreover, the effect of the pH and mobile phase ratio on the capacity factors was analyzed and the pKa value of the FVP was determined chromatographically as 5.03 ± 0.02.

In this study, the acid dissociation constants (pKa) of three indicators, bromocresol green, phenolphthalein and methyl orange, were determined by scanning the solution of indicators and deposited pH paper in these solutions (in each step of color-changing solution) and then chemometrics method. These methods are simple, fast, and inexpensive. For this reason, first, the vessels containing the indicator solution and pH paper (in each step of color-changing solution) were scanned by the scanner, and then the images of sample solutions and pH papers were transferred to a computer using Microsoft Photo Editor (Microsoft XP). RGB values were measured, in each pixel, with the image processing tool box of MATLAB. In MATLAB (2013) software, a novel program was written based on RGB values, for calculating pKa indicators. The agreement between obtained pKa by this method and values reported in the literature demonstrates the utility of the method here used.

Acid dissociation constant value (pK a) is key parameter for predicting the extent of the ionization of a drug molecule at different pH. The effect of the mobile phase composition on the acid dissociation constant values was studied by measuring the pK a values at different acetonitrile concentrations, ranging from 25 to 35 % (v/v). pK a values and limiting retention factors of SSZ were calculated chromatographically using equations derived. From calculated pK a values, the aqueous pK a values of SSZ were calculated by various approaches. Moreover, the correlation established between retention factors and the pH of the water-acetonitrile mobile phase was used to determine the optimum separation condition. Optimized condition was also validated with respect to system suitability, linearity, precision, accuracy, limit of detection and limit of quantitation, respectively. A Gemini NX C18 column (250 × 4.6 mm I.D., 5 µm particles) was used for all the determinations.

In this study, the direct determination of cefixime as an anti-bacterial agent, in pharmaceutical formulations, urine and human blood plasma was conducted based on spectrophotometric measurements using parallel factor analysis (PARAFAC) and partial least squares (PLS). The calibration set was composed of fourteen solutions in the range of 0.50- 9.00 mg mL-1. PLS models were calculated at each pH applied to determine a set of synthetic cefixime solutions. The best model was acquired at pH 1.02 (PLS-pH 1.02). The ability of the method for the analysis of real samples was considered by determination of cefixime in pharmaceutical preparations, urine and plasma with satisfactory results. The calculated model with PARAFAC showed good prediction capability with root mean square error of prediction (RMSEP) of 0.12 for cefixime. The acid dissociation constants (pKa) of cefixime play a fundamental role in the mechanism of activity of cefixime. The pKa of cefixime were estimated by DATAN program using the corresponding absorption spectra-pH data. The calculated pKa values of cefixime were 1.89 and 3.80 for pKa1 and pKa2 respectively.

The acid dissociation constant values of some 2-(3H)-benzoxazolone derivatives were determined in buffered solutions by using the UV-Vis spectrophotometric method. These compounds have benzoxazolone core structures with arylpiperazine substituents and have been investigated for their anti-inflammatory and analgesic activities. The 2-(3H)-benzoxazolone derivatives showed acid dissociation constant values ranging from 8.26 to 9.28. The 5-chloro-2-(3H)-benzoxazolone derivatives exhibit higher acidity than the 2-(3H)-benzoxazolone derivatives. Additionally, a comparison of  5-chloro-2-(3H)-benzoxazolone derivatives showed that derivatives with halogen-containing R2 groups exhibited higher acidity. The findings of this study also suggest that UV–Vis spectrophotometry is one of the most effective techniques for measuring acid dissociation constant values.