Improved techniques for the photometric determination of partition coefficients, with particular reference to the...

Accurate partition coefficients K = Corg/Caq in chloroform-ammonia can be obtained by measuring the absorbance of the aqueous layer, replenishing with fresh aqueous solvent, and remeasuring the absorption after reequilibration. Provided the solute has a reasonably strong UV absorption, only 0.1-5 mg of material is required. Neither the amount, the extinction coefficient, nor (in most cases) the purity of the substrate material need be known. In general, K values ranging from 100 to 0.01 can be measured with a precision of greater than or equal to 10%. A detailed analysis of the absorbance and volumetric error sources permits the optimum combination of experimental conditions such as volume ratios, cell lengths, and absorbance (either direct or differential, or with scale expansion) to be predicted a priori. Quantitative estimates for all primary error sources, such as photometric precision, baseline error, stray light, and volumetric errors were also experimentally determined. The theoretical error model was tested by determining K for aniline under widely ranging experimental conditions and by comparing the experimental standard deviations with those calculated from the theoretical model. The agreement was found to be satisfactory. The method described appears to be of particular usefulness for the determination of extraction or chromatographic parameters of basic drugs.