Interlaboratory study of log P determination by shake-flask and potentiometric methods

J Pharm Biomed Anal. 1996 Aug;14(11):1405-13. doi: 10.1016/0731-7085(96)01773-6.

Abstract

The pKa and log P values of 23 structurally diverse compounds, including well known drugs and two pharmacons under development, were determined by potentiometry. Also, the log P data were measured by the shake-flask method. Many of the samples were investigated at both of the participating laboratories in order to evaluate the reproducibility of the pH-metric log P technique. The interlaboratory evaluation of pKa and log P data obtained by potentiometry showed excellent agreement (average delta pKa = +/-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 PpH-metric = 0.9794 log Pshake-flask -0.0397 (r = 0.9987, s = +/-0.091, F = 8153). The advantages of potentiometric log P determination are discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hydrogen-Ion Concentration
  • Laboratories / standards*
  • Methanol
  • Pharmaceutical Preparations / chemistry*
  • Potentiometry / methods
  • Potentiometry / standards
  • Solubility
  • Water

Substances

  • Pharmaceutical Preparations
  • Water
  • Methanol