Bromadiolone poisoning: LC-MS method and pharmacokinetic data

Area of Science:

• Toxicology
• Pharmacokinetics
• Analytical Chemistry

Background:

• Superwarfarin poisoning, including bromadiolone, presents a significant public health concern with high mortality rates.
• Limited human pharmacokinetic data exists for bromadiolone, especially following repeated exposures.

Purpose of the Study:

• To develop and report a validated analytical method for quantifying bromadiolone in human whole blood.
• To determine the pharmacokinetic profile of bromadiolone in a human patient following repeated exposure.
• To assess the stability of bromadiolone in whole blood samples under specific storage conditions.

Main Methods:

• Development of a liquid chromatography-mass spectrometry (LC-MS) method for bromadiolone quantification in whole blood.
• Analysis of serial whole blood and plasma samples from a 62-year-old woman with bromadiolone poisoning.
• Determination of bromadiolone half-life and plasma/blood ratio.
• Evaluation of bromadiolone stability in whole blood following freeze-thaw cycles.

Main Results:

• The LC-MS method achieved a limit of detection of 0.005 mg/L and a limit of quantification of 0.01 mg/L.
• Estimated bromadiolone half-life was approximately 6 days (initial phase) and 10-13 days (terminal phase).
• The mean plasma/blood ratio of bromadiolone was determined to be 1.7 ± 0.6.
• Bromadiolone concentrations decreased in whole blood samples after two freeze-thaw cycles, indicating instability.

Conclusions:

• A reliable LC-MS method for bromadiolone quantification in human blood has been established.
• The study provides crucial human pharmacokinetic data, including elimination half-life and plasma/blood distribution, for bromadiolone.
• Findings highlight the need for careful sample handling due to observed instability of bromadiolone in whole blood.