Partition Coefficients in Octanolwater Systems

One way, and perhaps the only one, to validate the partition coefficients measured by the CPC method is to compare them with "good" literature values measured by the conventional SF method. With the "normal mode" operation procedures, each compound was measured at least in triplicate and three measurements usually took no more than 2 hours. It would surely take much longer with "reversed mode" operation procedures. Among the compounds examined, which included alcohols, benzenes, phenols, anilines, benzamides, acetanilides, benzoic acids, benzenesulfonamides, amino acids, nucleosides, etc., excellent correlations between the partition coefficients measured by the two methods were found [10]:

log Pfcl = 0.99 (± 0.01) log pcrc _ o.Ol (± 0.02) (5)

where n is the number of compounds including model compounds and drugs, r is the correlation coefficient, and s is the standard deviation of the regression. The values in parentheses are the 95 % confidence limit of regression coefficients. These results have demonstrated the applicability of the CPC method for measuring partition coefficients. Since the precision of the obtained log P values depends much on the difference between tR and t0, our experience has shown that the CPC method is limited to compounds with log P values between ca. -3 and 3 [18]. Beyond this range, the solute elutes some seconds later than the nonretained compounds, resulting in large errors in the calculation of partition coefficients. While different modes of operation such as the interchange of operation modes could enlarge the range of measurable log P values, these methods are rather tedious and likely to impose additional errors.

The octanol phase is relatively viscous and the maximal proportion of stationary phase with a flow rate of 0.5-1 m/min is usually 87-90 %. Because the mutual solubility of the two phases could be increased at an elevated temperature, risking a loss of stationary phase during operation, the temperature in the centrifuge should be suitably regulated with ventilation or refrigerating systems. It is also necessary to control the dead time after several hours of operation since a change in t0 may occur due to loss of stationary phase or a rise in phase solution temperature.

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