Forced degradation and stability-indicating capability

A purity method that cannot separate a compound from its degradation products is not stability-indicating, and a stability claim made with a non-stability-indicating method is worthless. Forced degradation is how you find out which you have.

Stress conditions

The target is 5–20 % degradation. Below that the degradants may not be detectable; above it, secondary degradation products of the primary degradants confuse the picture and the mass balance stops closing.

Demonstrating stability-indicating capability

1. Each major degradant must be resolved from the main peak with R ≥ 1.5, and from each other where possible.
2. Peak purity of the main peak by PDA or MS must be maintained in every stressed sample — no degradant hiding underneath it.
3. Mass balance must close: the sum of the remaining main peak and all degradants should account for 95–105 % of the initial main-peak area, allowing for response-factor differences.
4. The method must show no interference from the diluent, the stress reagent, or the neutralisation.

What forced degradation tells the index

Two useful things. First, it identifies each compound's degradation pathways, which is what the "known degradants" field on every compound page records — and that in turn is what allows a submitted impurity to be classified as a storage finding rather than a synthesis finding. A des-Gly deletion sequence does not form in a vial; a methionine sulfoxide does. That distinction determines whether a poor result is the supplier's problem or the shipping route's.

Second, it sets the expectation for what a stressed lot looks like. When a submitted report shows a degradant profile matching a known oxidative pathway with nothing else out of place, the most likely explanation is exposure rather than manufacture, and the index says so on the record.