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Low Endotoxin Recovery—Masking of Naturally Occurring Endotoxin

1
Microcoat Biotechnologie GmbH, Am Neuland 3, 82347 Bernried am Stanberger See, Germany
2
LPS (Laboratory Program Support) Consulting Office, Tokyo 160-0023, Japan
3
Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo 113-8431, Japan
4
Institute of Physical and Theoretical Chemistry, University of Regensburg, 93040 Regensburg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(4), 838; https://doi.org/10.3390/ijms20040838
Received: 10 December 2018 / Revised: 8 February 2019 / Accepted: 12 February 2019 / Published: 15 February 2019
(This article belongs to the Section Molecular Toxicology)
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Abstract

Endotoxins are cell wall components of Gram-negative bacteria. A release of endotoxins into the human blood stream results in an inflammation reaction that can lead to life-threatening conditions like sepsis. Therefore, control for endotoxin contamination of intravenously administered drugs is crucial. Drugs are usually tested for putative endotoxin contamination with Limulus-based tests. However, validity of the compendial test procedures is questioned in the case of low endotoxin recovery (LER). To assure validity, regulatory authorities request hold-time studies of endotoxin in addition to pharmacopoeial requirements. Within these studies, endotoxin is added (spiked) to an undiluted product. The spiked product is held for a certain period of time and subsequently diluted for endotoxin determination. Due to the known heterogeneity of endotoxin the question has been raised as to which source represents the most adequate endotoxin spike. In the present study, endotoxin hold-time studies were analyzed by using different sources of endotoxin. Highly purified endotoxin, crude endotoxin extracts (Naturally Occurring Endotoxin) from different bacterial species and varied growth conditions as well as endogenous endotoxin contaminations were investigated. The results clearly demonstrate that endotoxin masking—an effect of LER—is dependent on the endotoxin source used. Various parameters such as bacterial strain and growth conditions lead to different masking susceptibilities. Due to these effects it is impossible to predict the susceptibility of bacterial endotoxin contamination to LER. In order to determine whether a sample is prone to LER, an endotoxin spike that is susceptible to LER is required. View Full-Text
Keywords: low endotoxin recovery; endotoxin; lipopolysaccharide; limulus amoebocyte lysate; naturally occurring endotoxin; bacterial endotoxin testing; masking low endotoxin recovery; endotoxin; lipopolysaccharide; limulus amoebocyte lysate; naturally occurring endotoxin; bacterial endotoxin testing; masking
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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MDPI and ACS Style

Reich, J.; Weyer, F.A.; Tamura, H.; Nagaoka, I.; Motschmann, H. Low Endotoxin Recovery—Masking of Naturally Occurring Endotoxin. Int. J. Mol. Sci. 2019, 20, 838.

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