Different Aggregation State
Most of the compounds encountered in pharmaceutical analysis are weak
acids or bases and their solubility characteristics depend upon their ionic
form (molecular species being more soluble in nonpolar, organic solvents
and the ionic species being more soluble in polar especially aqueous solvents).
Neutral or unionized compounds can be extracted from aqueous solutions
while ions cannot. When a drug exists in its ionized form, it can be converted
to the unionized form by altering the pH of the medium in which the drug
Partition coefficient as a function of pH
Many drugs are acids or bases that dissociate in aqueous solution. Changing
the pH of the aqueous solution alters the ratio between the ionized and
unionized form of the drugs. Since it is the unionized form which is extracted
into the organic phase, the fraction extracted will vary with pH of the
In aqueous buffer:
The partition between organic and aqueous buffer can be described by
a "true" partition coefficient, PC, as:
In lab you will be measuring an apparent partition coefficient, PC',
which will vary with pH or [H3O+]. This apparent
partition coefficient is given by
The partition coefficient and pKa determination
It is possible to determine the pKa of the drug undergoing extraction
using the data generated in part B.1.
Using the equation:
and substituting PC.[HA]org for [HA]org and
Ka[HA]aq/[H3O+] for [A-]aq,
gives the following equation:
which simplifies to
This gives us an equation with PC' as function of [H3O+]
with two unknown parameters, PC and Ka. This can be converted into a straight
line equation by taking the reciprocal of both sides of the equation.
Therefore plotting 1/PC' versus 1/[H3O+] should
give a straight line with a slope of Ka/PC and an intercept of 1/PC.