The pH-dependence in the partitioning behaviour of (RS)-[3H]propranolol between MDCK cell lipid vesicles and buffer. 
The pH-dependent partitioning of (RS)-[3H]propranolol between unilamellar vesicles of MDCK cell lipids and buffer was determined.  Partitioning studies were performed by means of equilibrium dialysis at 37 degrees C between pH 7 and 11 at a molar propranolol/lipid ratio in the membrane of 10(-6).  The partition-pH diagram was bell-shaped.  The highest apparent partition coefficient was 1797 at pH 9.7, the lowest was 805 at pH 6.9.  Curve fitting with a combination of Henderson-Hasselbalch equations revealed an inflection point at the apparent pKa of propranolol, i.e. 9.7, and two additional pKa values at pH 7.7 and 10.0.  The first one corresponds to the pKa of free fatty acids (FFA) within lipid bilayers and the other one to the pKa of phosphatidylethanolamine (PhE).  The true partition coefficients (P) of the neutral as well as the ionised solute were fitted for each ionisation status of the membrane.  The highest P, i.e. 2123, was calculated for neutral propranolol in the membrane with deprotonated FFA and protonated PhE. The partitioning behaviour of (RS)-[3H]propranolol in a complex membrane/buffer system can be described when considering ionisation changes of drug and lipids.