Endotoxin Testing
Quality control testing for bacterial endotoxins (lipopolysaccharides) in injectable products. Endotoxin contamination can cause fever, inflammation, and life-threatening reactions. The LAL test is the standard method. Injectable peptide products must meet strict endotoxin limits set by pharmacopoeias.
Technical Context
Bacterial endotoxins (lipopolysaccharides, LPS) are the primary pyrogen concern for parenteral peptide products. LPS consists of: lipid A (the toxic component, embedded in the bacterial outer membrane), core polysaccharide, and O-antigen. Even nanogram quantities can cause fever, hypotension, and potentially fatal septic shock. LAL testing methods: gel-clot (qualitative — detects above/below a specified limit), turbidimetric (quantitative — measures turbidity increase from LAL clotting reaction), and chromogenic (quantitative — measures colour change from chromogenic substrate cleavage). Recombinant Factor C (rFC) assay is a newer alternative that avoids harvesting horseshoe crab blood. Endotoxin limits (USP/EP): for IV drugs, generally ≤5 EU/kg body weight/hour; for intrathecal drugs, ≤0.2 EU/kg. Depyrogenation of manufacturing equipment uses dry heat (≥250°C for ≥30 min) or chemical treatment.