Sensitive method for endotoxin determination in nanomedicinal product samples

Nanomedicine (Lond). 2019 May;14(10):1231-1246. doi: 10.2217/nnm-2018-0339.


Aim: Nanomaterials and nanomedicinal products tend to interfere with various commonly used assays, including regulatory required endotoxin detection methods for medicines. We developed a method to quantify endotoxin levels that is compatible with nanomaterials and nanomedicinal products. Materials & methods: The method is based on measuring endotoxin indirectly via 3-hydroxylated fatty acids of lipid-A, using Ultra High Performance Liquid Chromatography coupled with mass spectrometry. The outcome was related to results of the commonly used Limulus Amebocyte Lysate method. Results: The ultra high performance liquid chromatography coupled with mass spectrometry method has clear advantages compared with other endotoxin determination assays; particularly the absence of nanospecific interference. Conclusion: The method is sensitive, straightforward and accurate in determining and quantifying endotoxin in nanomedicinal product samples.

Keywords: LAL assay; fatty acids; interference; lipopolysaccharide; nanomaterials; nanomedicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Assay
  • Cerium / chemistry
  • Chromatography, High Pressure Liquid
  • Dendrimers / chemistry
  • Fatty Acids / analysis
  • Ferric Compounds / chemistry
  • Lipopolysaccharides / analysis*
  • Liposomes / chemistry
  • Membrane Proteins / chemistry
  • Nanomedicine
  • Nanostructures / chemistry*
  • Particle Size
  • Tandem Mass Spectrometry
  • Titanium / chemistry


  • Dendrimers
  • Fatty Acids
  • Ferric Compounds
  • Lipopolysaccharides
  • Liposomes
  • Membrane Proteins
  • endotoxin binding proteins
  • titanium dioxide
  • ferric oxide
  • Cerium
  • ceric oxide
  • Titanium