Endotoxin.

Bacterial cell-wall components that can cause harmful reactions.

Endotoxins are lipopolysaccharide components of the outer membrane of gram-negative bacteria. They are released when those bacteria die and break apart, and the human immune system detects them at extremely low concentrations, mounting a strong inflammatory response that can include fever, chills, and in serious cases a dangerous drop in blood pressure. This is why endotoxin is a specific and separately tested quality concern for anything intended for injection. The property that makes endotoxin distinctive is that it is not alive, so killing the bacteria does not remove it. Standard sterilization can produce a preparation with no viable organisms that still contains enough endotoxin to cause a reaction, and endotoxin is notably heat-stable, surviving conditions that destroy the bacteria themselves. Removing it requires deliberate steps during manufacturing rather than a terminal sterilization step. Pharmaceutical manufacturers test for it using established limulus-based assays and work to defined limits. The point that matters for this field is that a Certificate of Analysis showing high chemical purity says nothing about endotoxin unless endotoxin testing is explicitly listed on it, and research-grade material is typically not manufactured or released against injectable endotoxin limits at all. Purity and pyrogen-free are different claims.