Automated techniques in pK a determination: Low, medium and high-throughput screening methods.

Drug discovery programs that generate hundreds of new molecular entities need efficient methodologies for physicochemical profiling. Several high-throughput methods for pK _a screening have been developed in the last 15 years to determine this key physicochemical parameter. Separation techniques such as HPLC-MS or capillary electrophoresis are particularly well-suited due to their high throughput and capacity to deal with impure or complex samples. In addition, potentiometric and (mostly) UV-metric-based methods (plate-based and automated systems), find their place as very precise methodologies for pK _a determination despite of somewhat lower throughput. Finally, pK _a prediction software packages are useful estimator tools but, to date, they cannot replace experimental measurements when accurate pK _a values are required.
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