PhD Scientific Days 2025

Poster Session III. - H: Pharmaceutical Sciences and Health Technologies

Evaluating Acid/Base Constant Determination Methods: A Meta-Analysis of Orthogonal Techniques

Name of the presenter

Pálla Tamás

Institute/workplace of the presenter

Department of Pharmaceutical Chemistry

Authors

Tamás Pálla¹, Arash Mirzahosseini¹

1: Department of Pharmaceutical Chemistry

Text of the abstract

The determination of acid/base equilibrium constants is fundamental in understanding chemical speciation, drug behavior, and complex formation in solution. Multiple analytical techniques—such as pH-potentiometry, NMR, and UV–Vis spectrophotometry—are used for measuring protonation constants, each with unique advantages and limitations. However, discrepancies in the reported values across methods and laboratories raise concerns about reproducibility and method-dependent bias, necessitating a systematic evaluation of these techniques.
This study aims to assess the accuracy and consistency of protonation constant determination by comparing two widely used experimental techniques—pH-potentiometry, and NMR spectroscopy titration—through a meta-analytical approach.
Meta-analysis was applied to both new and previously published data, incorporating statistical evaluations such as Bland–Altman plots and mixed-effect general linear models. The effects of temperature, ionic strength, and data processing approaches were considered across methods.
The study found that, while good overall agreement exists between methods, systematic deviations of up to 0.2–0.3 pKa units were observed for certain compounds. NMR often showed slightly lower pKa values compared to potentiometry, particularly for multiprotic systems where overlapping equilibria may affect resolution. Statistical analysis revealed that no single method was universally superior, but method-specific sensitivities and artifacts can lead to deviations in complex systems.
The comparison highlights the necessity of multi-method validation in the determination of acid/base constants, especially for drug-like compounds. While each technique is robust within its operational limits, the integration of orthogonal methods enhances confidence in reported values.
This research was supported by the EKÖP-2024-61 New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.