INTERLABORATORY STUDY OF LOG-P DETERMINATION BY SHAKE-FLASK AND POTENTIOMETRIC METHODS

The pK(a) and log P values of 23 structurally diverse compounds, inclu ding well known drugs and two pharmacons under development, were deter mined by potentiometry. Also, the log P data were measured by the shak e-flask method. Many of the samples were investigated al both of the p articipating laboratories in order to evaluate the reproducibility of the pH-metric log P technique. The interlaboratory evaluation of pK(a) and log P data obtained by potentiometry showed excellent agreement ( average Delta pK(a) = +/- 0.02 and Delta log P = +/- 0.07). The log P values obtained by the two different methods, ranging from -1.84 to 5. 80 (nearly eight orders of magnitude), were in very good concordance, as shown by the linear regression analysis: log P-pH-metric = 0.9794 l og P-shake-flask -0.0397 (r = 0.9987, s = +/- 0.091, F = 8153). The ad vantages of potentiometric log P determination are discussed.