Measurements based on Separation

Many different types of chromatographic methods have been used to determine pKa value, such as ion-exchange chromatography, gas chromatography, and RP-HPLC, is well placed for high-throughput analysis. A review by Hardcastle et al. [21] explains the theory behind the calculations and the derivation of equations for the determination of pKa value. It has been demonstrated that the correct determination of pH of the mobile phase is key to the determination of pKa value of an analyte from chromatographic retention [22, 23]. However, this is the pKa value of the analyte in the mobile-phase system and not in a purely aqueous environment. 

The dielectric constant of cosolvent/water mixtures is less than that of water alone and therefore the extent of ionization and the associated ionization equilibria are suppressed  

High-Throughput logD74 Versus Shake-Flask logD7.4 

Alternative Methods lor Determining High-Throughput logDpH 

Sirius Analytical has developed a commercially available Profiler LDA instrument in which a proprietary stationary phase is coated with octanol. Octanol-saturated mobile phase is recirculated to maintain the octanol content of the stationary phase as constant. This system gives a dynamic range that covers — 1 log P 5. 

---