Development of an N-shaped cell for two-phase partitioning

We developed an N-shaped partition cell to measure the logarithm of partiti on coefficients between 1-octanol and water (log P-ow). The cell enabled us to measure the concentrations of the solute in the two phases periodically by HPLC without any tedious or time-consuming steps. The equilibrium time in the cell was almost 4 hours, and the obtained log P-ow values were consi stent with those by the conventional shake-flask method for neutral compoun ds with 1.1 < log P-ow < 3.8. This approach was applied to a monovalent bas ic drug, verapamil, and the dependence of log P-ow on the pH was measured u sing six cells simultaneously. The obtained pK(a) and log P-ow values of ve rapamil by the N-shaped cell method were in agreement with those by the sha ke-flask method; the analysis time was alsomst 7 hours. The cell was used i n an HPLC autosampler, and the whole operation for measuring log P-ow was p erformed automatically in combination with HPLC.