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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
Pharmaceutical chemistry
Drug development
Issue Date: 17-Dec-2015
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:
It is part of: Journal of Pharmaceutical and Biomedical Analysis, 2015, vol. 127, p. 26-31
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ISSN: 0731-7085
Appears in Collections:Articles publicats en revistes (Enginyeria Química i Química Analítica)

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