RPTLC determination of logPof structurally diverse neutral compounds

Autor: Krisztina Takacs-Novak, Vámos J, Katalin Deák, Gergely Völgyi, Klára Valkó
Rok vydání: 2008
Předmět:
Zdroj: Journal of Planar Chromatography – Modern TLC. 21:143-149
ISSN: 1789-0993
0933-4173
DOI: 10.1556/jpc.21.2008.2.12
Popis: A validated reversed-phase thin-layer chromatographic (RPTLC) method is proposed for parallel estimation of the lipophilicity of chemically diverse neutral compounds or weak acids and bases. To cover a wide range of lipophilicity two optimized chromatographic systems were used - one for determination of log P of low or moderately lipophilic compounds (log P = 0-3) and one for highly lipophilic compounds (log P = 3 6). RP-diC1 silanized silica gel plates were used as stationary phase. Mixtures of water with acetone, acetonitrile, methanol, ethanol, l-propanol, 2-propanol, and 1,4-dioxane were investigated as mobile phases. Acetone-water mixtures were found to be optimum for both systems in respect of correlation of RM values with octanol-water partition coefficients. Two chemically diverse sets of calibration compounds were selected to cover ranges of moderate and high lipophilicity. Correlation between log P and chromatographic RM data (log P = aRM + b) was good for both systems; the correlation coefficients (r) of the calibration equations were >0.99. The universal applicability of the optimized chromatographic systems was then tested using 20 randomly selected structurally diverse compounds. There was usually good agreement between log P values obtained by the shake-flask method and by RPTLC. This validated RPTLC method can be regarded as a suitable alternative for rapid and acceptably accurate estimation of the lipophilicity of drug candidates in the early phase of drug research.
Databáze: OpenAIRE
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