Endotoxin removal from protein solutions

J Biotechnol. 2000 Jan 21;76(2-3):97-119. doi: 10.1016/s0168-1656(99)00185-6.


Endotoxins liberated by gram-negative bacteria are frequent contaminations of protein solutions derived from bioprocesses. Because of their high toxicity in vivo and in vitro, their removal is essential for a safe parenteral administration. A general method for the removal of endotoxins from protein solutions is not available. Methods used for decontamination of water, such as ultrafiltration, have little effect on endotoxin levels in protein solutions. Various techniques described in the patent literature are not broadly applicable, as they are tailored to meet specific product requirements. Besides ion-exchangers and two-phase extraction, affinity techniques are applied with varying success. Also, taylor-made endotoxin-selective adsorber matrices for the prevention of endotoxin contamination and endotoxin removal are discussed for this purpose. After giving an overview of the properties of endotoxins and the significance of endotoxin contamination, this review intends to provide an overall picture of the various methods employed for their removal. Avenues are pointed out how to optimise a method with regard to the specific properties of endotoxins in aqueous solution.

Publication types

  • Review

MeSH terms

  • Adsorption
  • Animals
  • Biotechnology / methods*
  • Chromatography, Affinity
  • Chromatography, Ion Exchange
  • Endotoxins / chemistry
  • Endotoxins / isolation & purification*
  • Endotoxins / toxicity
  • Humans
  • Polymyxin B / chemistry
  • Polymyxin B / pharmacology
  • Proteins / chemistry*
  • Solutions
  • Ultrafiltration


  • Endotoxins
  • Proteins
  • Solutions
  • Polymyxin B