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cc-by-nc-nd (c) Elsevier B.V., 2015
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/100383

High-throughput log Po/w determination from UHPLC measurements: revisiting the chromatographic hydrophobicity index

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A fast and accurate lipophilicity determination is fundamental in the drug discovery process, as long as it is a relevant property in the absorption, distribution, metabolism, excretion and toxicity (ADMET) of a potential drug substance. In the present work, different models based on chromatographic retention values for a large set of compounds and some of their molecular descriptors (calculated by ACD/Labs or CODESSA programs) have been examined in order to establish reliable equations for log Po/w determination from fast chromatographic hydrophobicity index (CHI) measurements. This appears to be a very interesting high-throughput methodology for screening purposes, since CHI values can be measured by UHPLC in very short runs (<4 min) and molecular descriptors can be easily computed from the structure of any compound. The selected final descriptors were Abraham's hydrogen-bond acidity (A) and excess molar refraction (E) from ACD/Labs, and hydrogen-bond acidity HDCA-1/TMSA and HOMO-LUMO polarizability descriptors from CODESSA software. The proposed equations allow an accurate determination of log Po/w with standard errors in the range of 0.4 units.

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SUBIRATS I VILA, Xavier, ROSÉS PASCUAL, Martí, BOSCH, Elisabeth. High-throughput log Po/w determination from UHPLC measurements: revisiting the chromatographic hydrophobicity index. _Journal of Pharmaceutical and Biomedical Analysis_. 2015. Vol. 127, núm. 26-31. [consulta: 29 de gener de 2026]. ISSN: 0731-7085. [Disponible a: https://hdl.handle.net/2445/100383]

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