oxidation

Oxidation is degradation driven by oxygen and the reactive species it spawns — the same chemistry that turns butter rancid and browns a cut apple. The drug loses electrons (or gains oxygen), and its molecular structure is altered, usually with loss of potency and sometimes a tell-tale colour change.

Pharmaceutically, the dominant route is autoxidation: a self-propagating chain reaction in which trace initiators create free radicals that react with atmospheric oxygen, generating more radicals. Easily oxidised groups include phenols, catechols, thiols, aldehydes and unsaturated fats. Crucially, the chain is hugely accelerated by trace transition metals (iron, copper) and by light and heat, so vanishingly small contaminants can do large damage.

Defences attack each link of the chain: antioxidants mop up radicals or are sacrificially oxidised in the drug's place; chelating agents lock up catalytic metals; nitrogen or argon purging and oxygen-impermeable packaging exclude the reactant; and amber glass or opaque containers block light. Often several measures are combined.

An honest caveat: oxidation is notoriously hard to predict and reproduce, because it hinges on trace metals and oxygen levels that vary between batches and laboratories. A formulation that looked stable in development can oxidise unexpectedly once scaled up with a different water supply or raw-material source.