Intravascular Residence Time Determination for the Cyanide Antidote Dimethyl Trisulfide in Rat by Using Liquid-Liquid...

Area of Science:

• Pharmacokinetics and Toxicology
• Analytical Chemistry

Background:

• Cyanide poisoning is a critical medical emergency requiring rapid and effective antidotes.
• Dimethyl trisulfide (DMTS) is a potential cyanide antidote, but its pharmacokinetic profile, specifically intravascular residence time, requires elucidation.

Purpose of the Study:

• To determine the intravascular residence time of dimethyl trisulfide (DMTS) in a rat model.
• To establish a reliable analytical method for quantifying DMTS in biological samples.

Main Methods:

• Development of a sample preparation method using liquid-liquid extraction with cyclohexanone.
• Quantification of DMTS using high-performance liquid chromatography coupled with ultraviolet absorption spectroscopy (HPLC-UV).
• Intravenous administration of DMTS to rats and serial blood sampling for pharmacokinetic analysis.

Main Results:

• A validated HPLC-UV method with a linear calibration curve (R² = 0.9994) for DMTS concentrations between 0.010 and 0.30 mg/mL.
• The method achieved a limit of detection of 0.010 mg/mL and a limit of quantitation of 0.034 mg/mL.
• The determined half-life of DMTS in rats was 36 minutes.

Conclusions:

• The developed HPLC-UV method is suitable for determining DMTS concentrations in rat blood.
• The 36-minute half-life of DMTS suggests adequate circulation time for its potential role as a cyanide antidote.