Analysis of potential cyanide antidote, dimethyl trisulfide, in whole blood by dynamic headspace gas chromatography-mass spectroscopy.

Cyanide is a rapidly acting and highly toxic chemical. It inhibits cytochrome c oxidase in the mitochondrial electron transport chain, resulting in cellular hypoxia, cytotoxic anoxia and potentially death. In order to overcome challenges associated with current cyanide antidotes, dimethyl trisulfide (DMTS), which converts cyanide to less toxic thiocyanate in vivo, has gained much attention recently as a promising next-generation cyanide antidote. While there are three analysis methods available for DMTS, they each have significant disadvantages. Hence, in this study, a dynamic headspace (DHS) gas chromatography-mass spectroscopy method was developed for the analysis of DMTS from rabbit whole blood. The method is extremely simple, involving only acidification of a blood sample, addition of an internal standard (DMTS-d₆) and DHS-GC-MS analysis. The method produced a limit of detection of 0.04 μM for DMTS with dynamic range from 0.2 to 50 μM. Inter- and intraassay accuracy (100 ± 15% and 100 ± 9%, respectively), and precision (<10% and <9% relative standard deviation, respectively) were good. The validated method performed well during pharmacokinetic analysis of DMTS from the blood of rats treated with DMTS, producing excellent pharmacokinetic parameters for the treatment of cyanide exposure. The method produced significant advantages over current methods for analysis of DMTS and should be considered as a "gold standard" method for further development of DMTS as a potential next-generation cyanide countermeasure.