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Title: | High-throughput log Po/w determination from UHPLC measurements: revisiting the chromatographic hydrophobicity index |
Author: | Subirats i Vila, Xavier Rosés Pascual, Martí Bosch, Elisabeth |
Keywords: | Química farmacèutica Desenvolupament de medicaments Solubilitat Pharmaceutical chemistry Drug development Solubility |
Issue Date: | 5-Aug-2016 |
Publisher: | Elsevier B.V. |
Abstract: | 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. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.jpba.2015.12.015 |
It is part of: | Journal of Pharmaceutical and Biomedical Analysis, 2015, vol. 127, p. 26-31 |
URI: | http://hdl.handle.net/2445/100383 |
Related resource: | http://dx.doi.org/10.1016/j.jpba.2015.12.015 |
ISSN: | 0731-7085 |
Appears in Collections: | Articles publicats en revistes (Enginyeria Química i Química Analítica) |
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