Defense Date
2025
Document Type
Directed Research Project
First Advisor
Matthew S. Halquist, Ph.D.
Second Advisor
Michelle R. Peace, Ph.D.
Third Advisor
D. Matthew Walentiny, Ph.D.
Abstract
Xylazine is a nonopioid veterinary sedative and an α2 adrenergic receptor agonist. It emerged in the opioid epidemic as an adulterant of illicit fentanyl. As xylazine becomes more involved in fatal overdoses, it is relevant to elucidate its biodistribution post-exposure due to its exacerbation of adverse events, namely respiratory depression, as xylazine’s contributions to existing adverse effects of synthetic opioids is understudied. A bioanalytical method to quantify xylazine and select metabolites in tissue using LC-QToF was validated and applied to a preclinical mouse model in order to characterize xylazine’s biodistribution in whole blood and six tissues at a dose known to induce respiratory depression in mice. Mice were dosed intraperitoneally (i.p.) at five distinct sampling times (5, 30, 60, 240, 360 minutes) prior to sacrifice in order to evaluate the time course of xylazine distribution. Xylazine is primarily distributed to the liver, kidneys, and stomach. The time course of drug distribution differed between xylazine and its metabolite xylazine glucuronide, with xylazine reaching the maximum concentration in each tissue much sooner on average compared to xylazine glucuronide. These findings suggest that metabolism begins soon after i.p. administration and that the effects of xylazine may be organ-specific.
Rights
© The Author(s)
Is Part Of
VCU Master of Science in Forensic Science Directed Research Projects
Date of Submission
5-23-2025