Impurity Profiling
The identification and quantification of all impurities present in a pharmaceutical product. For synthetic peptides, impurities include truncated sequences, deletion sequences, oxidation products, racemisation products, and residual reagents. Impurity profiles must be characterised and controlled within established limits.
Technical Context
ICH Q3A (drug substance) and Q3B (drug product) establish thresholds: reporting threshold (above which impurities must be reported in the specification — typically 0.05-0.1%), identification threshold (above which impurities must be structurally identified — typically 0.1-0.5% depending on daily dose), and qualification threshold (above which impurities must be toxicologically qualified — typically 0.15-1.0% depending on daily dose). For synthetic peptides, process-related impurities include: deletion peptides, truncated sequences, deprotection failures, racemised amino acids, aggregates, and residual reagents/solvents. Degradation-related impurities include: oxidation products (Met sulphoxide, Trp oxidation), deamidation products (Asp/isoAsp from Asn, Glu from Gln), hydrolysis products (cleavage fragments), and aggregation products. Forced degradation studies (ICH Q1A) — exposing the product to acid, base, oxidation, heat, light, and humidity — identify potential degradation pathways and validate the stability-indicating capability of analytical methods.