Page 69 - Quality control of pharmaceuticals (07-PA 704)

For other drugs, the toxicology of degradants is initially unknown. For
example, a degradant of tetracycline is epianhydrotetracycline, known to
cause Fanconi syndrome.
Sometimes, reactive intermediates are formed that are known or suspected
to be toxic.for example, penicillins rearrange under acidic pH conditions to
penicillenic acids, which are suspected to contribute to the allergenicity of
penicillins
2. Degradation of the drug may make the product esthetically unacceptable.
Products are presumed to be adulterated if significant changes in, for
instance, color or odor have occurred with time. For example, epinephrine
is oxidized to adrenochrome, a highly colored red material. Any
epinephrine-containing product that develops a significant pink tinge is
usually considered adulterated.

Pathways of Chemical Degradation
(1) Hydrolysis:

Hydrolysis means the reaction of a molecule with water resulting in the cleavage of
a chemical bond within that molecule. Although there are a large number of
functional groups that are susceptible to hydrolysis, esters and amides are the most
common ones found in drugs prone to hydrolysis.
Hydrolysis reactions occur quite slowly, but, in the presence of acid or alkali, the
rate of the reaction increases and significant decomposition can occur.
It should be remembered that many drugs are amines, which can be rendered water-
soluble by formation of their hydrochloride salt.
Salts of weak bases and strong mineral acids are acidic by partial hydrolysis and the
H+ formed by hydrolysis of the salt can catalyse hydrolysis reactions on the drug
itself.