Step-1: Classify the peak by origin
- Metabolite +Degradation ptoduct (e.g.: Related compound A)
- Formulation interaction product (e.g., lactose/ glucose/ galactose adducts)
- Unknown degradant
- Process impurity
- Artefact (sample preparation, diluent, filter, vial, handling etc.)
Step-2: Map the dominant formation pathway and whether it’s avoidable
Amlodipine besylate tablets example:
- Degradation pathway: Related compound A is a photostability driven oxidative degradant. So, limit must reflect realistic formation under light exposure.
- Drug-excipient interaction: lactose/ glucose/ galactose adducts from via Millard-type pathway. They are formulation dependent and may be irrelevant if your formulation removes the trigger.
Step-3: Apply the correct regulatory ruleset + exposure thresholds
- Use ICH Q3B thresholds based on maximum daily dose.
- Add special logic where relevant:
- Metabolite context
- GTIs/ structural alerts
- Compendial expectations (if claiming compliance)
Step-4: Convert limits into analytical requirements
- Specificity + resolution, with orthogonal confirmation when risk is high.
- Sensitivity
- Reporting format/ decimal/ rounding rules (e.g., critical when spec if NMT 0.20% and ICH reporting threshold is 0.1%)
Step-5: Link each limit to control level (control strategy)
- Process parameters
- Excipient selection, specs
- Packaging
- Stability data and trending
Related: Pharmaceutical Impurities Calculator
Resource Person: Pearl Pereira Nambiar