Graduate Thesis Or Dissertation
 

Mass Spectrometry-based Analysis of Superwarfarins and their Metabolites and the Investigation of Novel Treatments for Poisoned Victims

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/5h73q362k

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  • Superwarfarins are anticoagulant rodenticides that are 100 times more potent and 15 times more persistent than warfarin. They have been used since the 1980s and cause over 10,000 cases of accidental and intentional poisonings per year. Apart from inducing uncontrollable bleeding, by inhibiting the vitamin K cycle, superwarfarins can disrupt metabolism, protein synthesis, membrane packing, and have shown to cause in vitro neuroinflammation and cytotoxicity. Here, we developed and validated two tandem mass spectrometry-based methods to evaluate the persistence of superwarfarin diastereomer pairs as well as their four stereoisomers using C18 reverse phase and chiral phase chromatography, respectively. The methods were applied to plasma samples from individuals who inhaled synthetic cannabinoid products tainted with superwarfarin rodenticides during the 2018 outbreak of coagulopathy. In response to the limited treatments available to counter superwarfarin induced coagulopathy, sequestration-based therapies, intralipid and cholestyramine, were evaluated. In consideration of the lack of superwarfarin metabolite studies in human biological matrices, and the potential utilization of cytochrome P450 inducers, the fragmentation pathways of standard superwarfarins were studied and used to identified and characterize several metabolites in human plasma from the 2018 outbreak.
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Related Items
  • van Breemen Laboratory Website
  • Separation and Quantification of Superwarfarin Rodenticide Diastereomers—Bromadiolone, Difenacoum, Flocoumafen, Brodifacoum, and Difethialone—in Human Plasma
  • Effects of vitamin K1 treatment on plasma concentrations of long-acting anticoagulant rodenticide enantiomers following inhalation of contaminated synthetic cannabinoids
  • Coagulopathy After Synthetic Cannabinoid Use: A Case Report
  • Should Cytochrome P450 Inducers be Used to Accelerate Clearance of Brodifacoum from Poisoned Patients?
Funding Statement (additional comments about funding)
  • NIH Grant T32AT010131 (Acquired by Dr. Richard B van Breemen and Dr. Taifo Mahmud at Oregon State University)
  • NIH Grant U01NS083457 (Acquired by Dr. Douglas Feinstein at the University of Illinois at Chicago)
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  • Ongoing Research
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  • 2020-09-03 to 2021-10-03

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