Recent advances in the identification and quantification of xylazine and medetomidine in biological specimens

Xylazine is a veterinary sedative that is frequently detected in the illicit drug supply, often found mixed with illicitly manufactured fentanyl (IMF). It has been detected in the blood of overdose victims and patients who use illicit drugs. Xylazine is not approved for use in humans. It is an alpha-2-adrenergic receptor agonist that causes deep sedation that is non-responsive to naloxone, the antidote for opioid overdose. Chronic exposure to xylazine has been linked to severe wounds that can progress to amputation. Medetomidine is another related veterinary sedative that has more recently emerged as an adulterant in IMF. Medetomidine is also an alpha-2-adrenergic agonist, and in veterinary medicine it is known to be significantly more potent than xylazine. The mixture of these drugs with IMF complicates the treatment of patients exposed to these drugs. Wider availability of analytical methods to detect xylazine, and now medetomidine, is crucial for responding to these health threats and increasing knowledge on the harms and potential therapies for exposed patients. This review covers what is currently known about these drugs, including observed concentrations in various biospecimens, expected major metabolites and windows of detection, and available analytical approaches for detecting exposure.