Chemistry Reference
In-Depth Information
A RI detector relies on changes in the refractive index of the mobile
phase as a solute elutes to detect a signal, while an ECD functions like a
little electrode to oxidise or reduce the analyte as it elutes. In either case,
before the determination of
P
is carried out, you should seriously consider
measuring
P
for another drug! My PhD supervisor had a saying: 'Never
make a compound you cannot name'; to that can be added the advice
'Never make a compound that cannot be detected by a UV detector'. Many
entertaining hours can be spent optimising HPLC systems with RI or ECD,
but if you want to finish before your children grow up, these methods of
detection are best avoided. There are some advantages to the HPLC method
of determining
P
, namely that HPLC does not require much sample and
that the sample does not have to be 100% pure. Also, once the complete
system has been obtained, the cost of the determination is limited to the
purchase of HPLC-grade solvents and electricity.
Drug absorption, distribution and bioavailability
The study of the fate of a drug administered to an organism is called
phar-
macokinetics.
This discipline involves measuring or predicting the
a
bsorp-
tion,
d
istribution,
m
etabolism and
e
xcretion
(usually known by the
acronym ADME) of the drug in the body. Pharmacokinetics has been
described as 'what the body does to the drug' as opposed to
pharmaco-
dynamics,
which is the study of mechanisms of drug action and the
biochemical changes brought about by treatment with the drug or 'what the
drug does to the body.' Some older textbooks use the expression 'molecular
pharmacology' instead of pharmacodynamics.
Bioavailability (symbol
F
) is a measure of the extent to which a drug
reaches the bloodstream and is available at its site of action. The bioavail-
ability of a drug administered by intra-venous (i.v.) injection is defined as 1
(since the entire dose is available in the systemic circulation). Problems start
to appear, however, if the drug is administered by a non-parenteral route
(e.g. oral, rectal, topical). In these cases, the bioavailability of a drug is
often considerably less than 1 due to a number of factors, such as poor
absorption from the gut (in the case of an oral medicine), extensive binding
to circulating plasma proteins, or rapid 'first pass' metabolism in the liver.
The most popular method of administering drugs and medicines, at
least in the UK, is the oral route. Tablets, capsules or oral liquids are swal-
lowed and, once in the stomach, the tablet or capsule disintegrates to release
the active drug molecule. Interestingly, a drug is not considered to be
in
the
body until it has been absorbed across the gut wall and into the blood-
stream. The gut can be thought of as a hollow tube running through the
