Endotoxin

Lipopolysaccharide fragments from the outer membrane of Gram-negative bacteria — heat-stable, biologically potent contaminants that chemical purity tests do not detect, measured by the LAL assay.

Endotoxins are lipopolysaccharide components of the outer cell membrane of Gram-negative bacteria, released when the cells die and break apart. They are heat-stable, survive conditions that kill the bacteria themselves, and are biologically active at very low concentrations, which is why endotoxin load is a standard release test for injectable pharmaceuticals.

The point that matters when reading a peptide certificate is that endotoxin is invisible to the chemical analyses the certificate usually contains. HPLC and mass spectrometry characterise the compound; they say nothing about microbial contamination. A vial can be 99% chromatographically pure and still carry endotoxin, because the two measurements answer unrelated questions.

The pharmacopoeial method is the bacterial endotoxins test using Limulus amoebocyte lysate (LAL), which reacts with endotoxin at picogram levels; recombinant reagents are increasingly accepted as animal-free equivalents. Endotoxin testing appears on research-compound certificates only when specifically commissioned, so its absence from a standard COA is normal — and is one of the stated limits of what such a certificate can establish.

SourceUSP — Bacterial endotoxins test (harmonised general method)

For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice.