reactive metabolite trapping

Reactive metabolites are short-lived, chemically aggressive molecules produced when the body breaks a drug down; they are too unstable to catch directly. Reactive metabolite trapping is a lab trick to catch them indirectly: you add a sticky 'bait' molecule that grabs any reactive species the instant it forms, freezing it into a stable, detectable product.

In a typical experiment, the drug is incubated with liver microsomes or cells that carry out metabolism, together with a trapping agent such as glutathione (which mimics the protein nucleophiles a reactive metabolite would otherwise attack). If reactive metabolites form, they bond to the trap, and the resulting adducts are detected and identified by mass spectrometry. Cyanide is sometimes used to trap a different class of reactive intermediates.

Finding trapped adducts flags a potential toxicity risk, because reactive metabolites are implicated in liver injury and idiosyncratic reactions, and points to which part of the molecule is being activated. That guidance lets chemists redesign the offending substructure. The caveat is that a positive trapping result signals a hazard, not a certainty of harm: the actual risk also depends on dose, clearance, and how much reactive metabolite forms in real life.