Analysis of Novel Cyanide Antidote Dimethyl Trisulfide for Pharmacokinetic Studies, and Sulfur Mustard Metabolites for Identification of Biomarker of Inhaled Dos

Cyanide poisoning by accidental or intentional exposure poses a severe health risk. The current FDA approved antidotes for cyanide poisoning can be effective, but each suffers from specific major limitations. Dimethyl trisulfide (DMTS), a sulfur donor that detoxifies cyanide by converting it into thiocyanate, is a promising next generation cyanide antidote. Although a validated analytical method to analyze DMTS is not currently available from any matrix, one will be vital for the approval of DMTS as a therapeutic agent against cyanide poisoning. Hence, a stir bar sorptive extraction (SBSE) gas chromatography -- mass spectrometry (GC-MS) method was developed and validated for the analysis of DMTS from rabbit whole blood. The limit of detection (LOD) using this method was 0.06 microM with dynamic range from 0.5 -- 100 muM. The method described here allows further investigations of DMTS as a promising antidote for cyanide poisoning.;Sulfur mustard (SM) is the most utilized chemical weapon in modern history. Although its exposure can result in wide range of toxic outcomes, airway injury leading to respiratory failure is the principal cause of mortality in victims. Therefore, current investigations are underway which focus on understanding the inhalation toxicity of SM in order to develop effective therapeutic interventions. A major challenge in inhalation studies is the quantification of actual respiratory dose. In this report, we identified biomarkers that have the potential for correlation to inhalation dose. Preliminary data for correlation of two biomarkers to dose are also presented. To our knowledge, there are no studies done in identifying SM biomarkers in inhalation exposure. Additionally, a rapid, simple, and direct GC-MS analysis technique for an important SM biomarker, sulfur mustard oxide (SMO), was developed and validated in swine plasma. The LOD of the method was 0.1 microM, with a linear range from 0.5 -100 microM. The availability of this method will allow easy and rapid diagnosis (within 15 min of exposure) of SM poisoning especially during the asymptomatic latency period (6-24 h post-exposure).