What are endotoxins?
Endotoxins, also known as lipopolysaccharides (LPS), are toxins produced by Gram-negative bacteria. They are released when the bacteria are killed or undergo cell lysis. LPS consists of three parts: lipid A, core polysaccharide, and O antigen. Lipid A is the toxic component responsible for triggering inflammatory and immune responses in mammals. Symptoms can vary from fever and inflammation to septic shock, depending on the dose and individual response. In pharmaceutical and medical contexts, LPS is a critical contaminant that must be carefully monitored and controlled to ensure the safety of drugs, medical devices, and biological products.
What are the recommended tests from USP and FDA?
The United States Pharmacopeia (USP) proposes the Limulus Amebocyte Lysate (LAL) assay
as the gold standard test for endotoxin detection. This assay utilizes lysate from the blood cells of the horseshoe crab Limulus polyphemus to detect the presence of endotoxins. Additionally, the FDA and USP have approved four basic methods for end-product release testing [1,2]:
- Gel-clot: A qualitative test where the formation of a gel clot in the presence of endotoxins indicates their presence. It’s relatively simple and inexpensive but less sensitive compared to other methods.
- Turbidimetric: A quantitative test that measures the turbidity produced by the reaction between endotoxins and a chromogenic substrate. It’s similar to the chromogenic method but relies on changes in turbidity rather than color.
- Chromogenic: A quantitative test where the color change produced by the reaction between endotoxins and chromogenic substrates is measured spectrophotometrically. It offers greater sensitivity and quantification compared to the gel-clot method.
- Colorimetric: Also, a quantitative test, similar to the chromogenic method. Endotoxins interact with a chromogenic substrate, causing a color change that can be measured spectrophotometrically. The intensity of the color change is directly proportional to the concentration of endotoxins in the sample.
Does Synoligo offer endotoxin testing and removal for oligos?
Yes, our manufacturing process is optimized with safety in mind, starting with certified raw materials and enforcing good lab practices at every step. Whether for research or pre-clinical testing, we guarantee endotoxin levels below 0.01 EU/mg for all our products. Our team can also meet specific endotoxin level requirements for your project and help clean up endotoxin-contaminated oligo products using our proprietary processes. Contact us for more questions!
References:
- https://www.usp.org/harmonization-standards/pdg/general-methods/bacterial-endotoxins
- https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/inspection-technical-guides/bacterial-endotoxinspyrogens