Abstract
Abstract A rapid, reliable and simple microscale method for the determination of octanol-water partition coefficients has been developed and evaluated. Rapid solute partitioning and facile octanol-water phase separation is accomplished in a commercially available mixer-separator device. The relative concentration of solute in each phase is then measured directly by computer-based reverse phase HPLC. The procedure requires only 10 μg of sample, which need not be pure, and uses 1 ml or less of both n-octanol and pH 7.0 phosphate buffer. Log P values of 26 compounds, mainly nucleoside analogues with anti-HIV and antitumor activity, have been determined in the range 0.7 to -2.4 with a precision better than ±0.04 log units. For compounds with literature data available, measured log P values are in good agreement (better than ±0.2 log units) with those values obtained by traditional “shake-flask” methodology. The described method is applicable to both single compound analysis and simultaneous multiple compound determinations through use of isocratic or gradient HPLC techniques.
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