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n 1997Valkó et al. developed a generic fast gradient HPLC method, based on the calculation of the Chromatographic Hydrophobicity Index (CHI) from the gradient retention times, in order to measure lipophilicity. We have employedthe correlations between CHI and log Po/wand adapted the rapid gradient HPLC method to UHPLC obtaining excellent resolution and repeatability in a short analysis time (<4min). log Po/wvalues can be easily obtained from these CHI measurementsbut, unfortunately, these correlations are only valid for non-ionized compounds. Consequently, in order to determine the effective log Po/wvalue at a particular pH, afast high-throughput method for pKadeterminationwas required. The IS-CE method, based on the use of internal standards (IS) and capillaryelectrophoresis(CE),is a fast and attractive alternative to other methods for pKadetermination,since itoffers multiple advantages compared to them: low amounts of test compounds and reagents are needed, high purity is not required, specific interactions between test compounds and buffers are corrected, etc. In addition, it allows the determination of a pKavalue in less than 5 minutes. Both CHI and IS-CE have beencombined in order to describe a high throughput alternative in thedetermination ofthe lipophilicity profiles of bioactive compounds

High throughput determination log Po/w/pKa/log Do/w of drugs by combination of UHPLC and CE methods