Intake and excretion of disodium monomethylarsonate in horses: a speciation study.

The study investigates the manner in which horses metabolize and excrete the drug disodium monomethylarsonate (DS-MMA(V)), using advanced spectroscopy techniques. The research suggests that the main way horses metabolize the drug into another compound, dimethylarsinic acid (DMA(V)), and excrete it primarily via urine. The study also found a significant increase in arsenic in the horses’ mane hair after administering the drug.

Methods and Approach

• Capillary electrophoresis coupled with inductively coupled plasma mass spectrometry was the primary technology utilized in this study. This method allows for the detailed examination of how DS-MMA(V) is processed within the horse’s body into different compounds (i.e., speciation) and how these are excreted.
• DS-MMA(V) was administered to horses via intramuscular injection for five consecutive days. The dosage contained 270 mg of arsenic each day.
• Urine, whole blood, plasma, and mane hair samples were collected and analyzed at various intervals: before the drug administration, during the administration period, and after the administration.

Findings

• The results demonstrated that the horse’s body quickly clears DS-MMA(V) from the blood and excretes it into the urine.
• The process followed the first-order kinetics model, with a biological half-life (time for the amount of drug in the body to reduce by half) of about 38 hours for urine and 44 hours for plasma.
• Dimethylarsinic acid (DMA(V)) was identified as the only metabolite (product of metabolism) of DS-MMA(V) present in the urine over nine days. Notably, four days after the final DS-MMA(V) administration, DMA(V) constituted up to 75% of the total arsenic species excreted – thus establishing the principal route of DS-MMA(V) metabolism in horses.
• Interestingly, even though DS-MMA(V) was only given for a brief five-day period, there was a significant increase (up to six times) in arsenic content in the newly grown mane hair of the horses.

Significance

• This study provides the first evidence of the body’s metabolic process of DS-MMA(V) in horses, contributing to the overall understanding of how this drug is processed and eliminated from the equine body.
• The unexpected discovery of increased arsenic in mane hair might suggest another route of excretion, or it could reflect the body’s efforts to sequester the compound. Further research is necessary to confirm and understand this response.