pKa Measurements / pI Measurements
Analysis of the acid dissociation constant and/or isoelectric point of a drug substance significantly influences compound solubility and membrane permeability. Measurement of this key physicochemical property is highly beneficial for support of ADMET (absorption, distribution, metabolism, excretion, toxicity) studies, product formulation, and analytical methods development. However, traditional methods for pKa measurement require relatively large amounts of pure compound, are sensitive to compound structure, and/or require complex data analysis procedures.
The pKa PRO™ system enables rapid, accurate, separation-based pKa measurements capable of detecting compound degradation or impurities while minimizing sample consumption and simplifying data analysis. It is the premier instrument for pka value determination
Key Benefits:
- The electrophoretic-based separation format of the pKa PRO™ provides the capability to identify and isolate compound degradants or impurities.
- Overall compound charge as a function of pH is displayed as well as the isoelectric point (pI). Data analysis is very intuitive and straightforward.
- Prediction of compound valency (number of pKa values present) is possible by relating compound mobility and molecular weight.
- The measurement of ionic mobility averts the need for intimate knowledge of sample concentration or the requirement of structure dependent changes in UV absorbance.
- Low sampling volumes and sensitive on-line UV detection minimize sample consumption and permit the measurement of sparingly soluble compounds.
- A co-solvent approach is available for measuring highly insoluble compounds.
- Saved results are stored in a data table for searchable access and are exportable in Excel™ format.
- The pKa PRO™ system can also be readily configured for performing log P measurements of neutral and basic compounds, chiral analysis and analytical scale small molecule separations.
The above plot shows representative pka value results for cefadroxil, a monobasic diacidic zwitterion with measured pKa values of 2.56, 7.24 and 9.67, and a corresponding pI value of 4.90. The plot displays the overall compound charge vs. pH. The predicted charge was +0.85 and -1.66, correctly indicating monobasic diacidic character.
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