An expert review on current approaches for endotoxin detection in various biological products

Abstract

End toxin is heat-stable lip polysaccharide (LPS) present in the outer membrane of the cell wall of Gramnegative bacteria. All parenteral preparations, as well as tissue implants, must be with no pyrogenic level of endotoxin or other related materials because of their associated health hazards and serious clinical effects. Accordingly, detection and limiting endotoxin in various pharmaceutical and biological products represent crucial issues. Rabbit pyrogen test (RPT) and Limulus Amebocyte Lysate (LAL) test are two methods used for endotoxin detection and quantification. Endotoxin detection is one of the most critical quality control tests required by the Food and Drug Administration (FDA) for all parenteral drugs in their final stage. Both in vitro LAL test and in vivo RPT can complement and reinforce each other but in certain cases, they are not interchangeable and they together provide a comprehensive picture of any potential contamination whether by endotoxin or any other pyrogenic matters.

Extraction and purification of lipopolysaccharide from Escherichia coli (local Isolate) and study its pyrogenic activity

“…The rabbit pyrogenic test was performed to evaluate the biological effect of the product, results showed that the mean rise of rabbit temperature was 1.4 °C which give the test a positive result and indicate the biological activity of the extra pure E. coli LPS and this agrees with (20,46). This elevation in animal's body temperature related to bacterial LPS which considered as a potent trigger for the immune system and capable to produce pro-inflammatory cytokine such as TNFα, IL1 as well as Prostaglandin E2 that mediated in the production of pyrogen reaction and appear its biological effect (16,20,21).…”

“…Rectal temperature before and after injection was recorded in all groups in the period interval of 30 mint up to 4 hours by using a medical rectal thermometer. The positive result was recorded as elevated in body temperature by 1-2 o C (20,26).…”

“…Bacterial LPS (endotoxin) consider as a potent pyrogen which means that have the ability to induce fever with several pathophysiological effects after injected intravenously; only a very small quantity (Nanogram/kg) of LPS was able to stimulate the response of an immune system and exaggerated host response to the removal of this toxic substance from body circulation by releasing many types of mediators that mediated in pyrogenic response. (20) the liberation of LPS from the cell wall in the host relates to a wide range of bad effects such as releasing of pro-inflammatory cytokine as TNF-α, IL-1 by macrophages which were responsible for fever production and lead to hyperthermia as a result of the pyrogenic response, and lead to inflammation, capillary leak, tissue toxicity ( 21) coagulation (22), aseptic shock, lethality (12). The aims of this study, is to extract and purify the LPS from E. coli local isolate, determine the molecular weight and pyrogenic effect of the extracted LPS (ELPS), and compare it with standard LPS(SLPS) purified from E. coli O55: B5 as a positive control.…”

Synthesis of MCM‐41@SO3H‐Polymixin B Nanocomposite for Extraction and Determination of Lipopolysaccharide from Aqueous Solutions using Taguchi Fractional Factorial Design

“…Using diverse types of chromatography such as gel filtration chromatography and ion-exchange chromatography, [17,18] employing ultrafiltration and microfiltration methods, [19,20] using affinity-based adsorbents, [21,22] which can be functionalized with substances such as polymixin B [23,24] and operating Triton X114 phase separation [25,26] are some of these processes. In addition, scientists can use biological detection techniques [such as Rabbit pyrogen test, [27,28] Limulus amoebocyte lysate assay [29,30] and bovine whole blood assay, [31,32] biosensor techniques, [33,34] aptamer-based methods, [35,36] electrochemical techniques, [11,37,38] fluorescence or luminescence techniques [39,40] and so on to measure the LPS values. In recent years, the use of nanoparticles as adsorbents with high ability and specificity in material extraction has been considered.…”

Extraction and characterization of Antigenic S- lipopolysaccharides Brucella abortus S99.

“…LPS typically consists of three different regions within different chemical and biological properties can be determined as follow: the lipid A (or endotoxin), a nonrepeating "core" oligosaccharide, and a distal O-specific polysaccharide O-PS or Oantigen (Raetz and Whitfield, 2002) In many Gram-negative infectious diseases, although the endotoxicity of lipid A is of great significance, the saccharide domains of naturally occurring LPSs noticeably are also significant in affecting the pathophysiology (Rittig et al, 2003). Endotoxin (LPS), a global thermo-resistant toxin present in the outer membrane of the cell wall of Gram-negative bacteria, which causes various life-threatening diseases at low doses (Li andBoraschi, 2016 andElkhateeb et al, 2019) As concern of serological diagnosis currently available, the major valuable antigen involved during vaccination and infection is the smooth LPS (Reyes et al, 2015). The outermost portion of LPS; O-chain (OPS) is an immunodominant antigen (Poester et al, 2010).…”