title: Rapid detection of bacterial endotoxins in ophthalmic viscosurgical device materials by direct analysis in real time mass spectrometry.
abstract: Bacterial endotoxins are lipopolysaccharides bound to the bacterial cell wall and released when bacteria rupture or disintegrate. Possible contamination of endotoxin in ophthalmic devices can cause a painful eye inflammation or result in toxic anterior segment syndrome after cataract surgery. Measurement of bacterial endotoxin in medical device materials is difficult since endotoxin binds with polymer matrix and some of the materials are very viscous and non-water soluble, where traditional enzyme-based Limulus amebocyte lysate (LAL) assay cannot be applied. Here we propose a rapid and high throughput ambient ionization mass spectrometric (MS) method using direct analysis in real time (DART) for the evaluation of endotoxin contamination in medical device materials. Large and structurally complex endotoxin instantaneously breaks down into low-mass characteristic fragment ions using DART and is detected by MS in both positive and negative ion modes. This method enables the identification and separation of endotoxin from medical materials with a detection limit of 0.03 ng mL-1endotoxins in aqueous solution. Ophthalmic viscosurgical device materials including sodium hyaluronate (NaHA), non-water soluble perfluoro-n-octane (PFO) and silicone oil (SO) were spiked with different known concentrations of endotoxin and analyzed by DART MS, where the presence of endotoxin was successfully detected and featured small mass fragment ions were generated for NaHA, PFO and SO as well. Current findings showed the feasibility of measuring endotoxin contamination in medical device materials using DART-MS, which can lead to a one-step analysis of endotoxins in different matrices, avoiding any potential contamination during sample pre-treatment steps.
authors: Division of Biology, Chemistry, and Materials Science, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, 20993, United States; Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biomedical Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
authors: Hongli
authors: H
authors: Li
authors: Division of Biology, Chemistry, and Materials Science, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, 20993, United States.
authors: Victoria M
authors: VM
authors: Hitchins
authors: Division of Biology, Chemistry, and Materials Science, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD, 20993, United States. Electronic address: Samanthi.Wickramasekara@fda.hhs.gov.
authors: Samanthi
authors: S
authors: Wickramasekara
mesh_terms: D001427:Bacterial Toxins / Q000032:analysis*; D004731:Endotoxins / Q000032:analysis*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D013508:Ophthalmologic Surgical Procedures / Q000295:instrumentation*
chemical_list: D001427:Bacterial Toxins; D004731:Endotoxins
keywords: Direct analysis in real time; Endotoxin; Mass spectrometry; Perfluoro-n-octane; Silicone oil; Sodium hyaluronate