Chemistry Reference
In-Depth Information
Organic (50ml)
Water (50ml)
[D]
org
66.7mg (2)
33.3mg (1)
[D]
aq
(unionised)
(unionised)
Figure 2.1
Simple partition law.
The percentage of drug extracted in the above example is simply given
by the mass of drug in the organic phase divided by the total mass of drug,
i.e. 66.7/100
66.7%.
The partition coefficient is an important piece of information as it
can be used to predict the absorption, distribution and elimination of
drugs within the body. Knowledge of the value of
P
can be used to predict
the onset of action of drugs or the duration of action of drugs, or to tell
whether a drug will be active at all. Part of medicinal chemistry, the
science of rational drug design, involves structure-activity relationships,
where the partition coefficient is used in mathematical equations that try
to relate the biological activity of a drug to its physical and chemical
characteristics.
In case this sounds too much like an advert for the partition coeffi-
cient, in reality the simple relationship above only applies if the solute in
question does not ionise at the pH of measurement. If the solute is a weak
acid or weak base (and a huge number of drugs are), then ionisation to
form an anion or a cation will considerably alter the solubility profile of the
drug. A fully ionised species will be much more soluble in water than the
unionised acid or base, and so the above ratio will vary depending on
the pH at which the measurement was carried out.
There are two ways round this problem: either the experimental
conditions are adjusted to ensure that the measured
P
is the partition coef-
ficient of the unionised molecule (this means that the
P
value for acids is
measured at low pH when the acid is unionised and, similarly, the partition
coefficient of a base is measured at high pH to prevent ionisation); or,
