Academy of Diagnostics & Laboratory Medicine - Scientific Short
Scientific Shorts are brought to you by the
The illicit drug supply in the United States (US) has become more volatile than ever before, contributing to the shift from an opioid epidemic to a polydrug crisis. At the forefront of this change have been novel psychoactive substances and cutting agents which contribute to unpredictable drug use patterns and associated morbidity and mortality. Cutting agents, or adulterants, are substances other than what is sold that are added to increase bulk, cut costs, enhance effects, and/or add new sensations. The most recent adulterant to pervasively affect the US illicit drug market is xylazine, prompting the US Government to designate it as an emerging threat (1).
Xylazine is a non-opioid veterinary sedative, not approved for human use, which has been reported primarily in the presence of fentanyl in the drug supply. Given the increasing trend of polydrug use, xylazine has made its way into drug mixtures containing stimulants and benzodiazepines as well. By November 2022, xylazine was reported in 48 out of 50 states, with prevalence exceeding 50% in some fentanyl laced samples (2,3). Because xylazine is not an opioid, naloxone does not reverse its effects. Patients exposed to opioids and xylazine may appear unresponsive due to persistent sedation, leading to potential mismanagement (e.g. excessive naloxone administration) or misdiagnosis. Cases of xylazine exposure masking benzodiazepine withdrawal have also been reported. Long-term users have been linked to withdrawal syndrome and necrotic ulcers sometimes necessitating amputation.
Recently, xylazine pharmacokinetic data in patients co-exposed to fentanyl and xylazine has become available, suggesting a longer half-life than initially thought (median of 12h, ranging from 6-21h), and identifying oxo-xylazine and sulfone-xylazine as key metabolites circulating in plasma for as long as xylazine (4). This is important, as detection of xylazine can elucidate cases of polydrug exposures that present diagnostic ambiguity.
What role can clinical laboratories play in detecting xylazine? Given the co-exposure with fentanyl, laboratories performing LC-MS/MS testing in house may consider adding xylazine in their urine fentanyl confirmation panels. Institutions that offer comprehensive drug screens by mass spectrometry should include xylazine in their panels. For institutions with no mass spectrometry available in house, an immunoassay for use on automated chemistry analyzers (currently for forensic use only) has recently been released with a cutoff of 10 ng/mL (5). Xylazine test strips (lateral flow immunoassays) are also available for forensic use only from multiple vendors, with cutoffs ranging from 100 ng/mL to 500 ng/mL(6).
Regulatory hurdles may present challenges in implementing xylazine testing. However, given the high prevalence among people who use drugs, and it’s devastating clinical effects, xylazine detection is a critical tool for clinical laboratories navigating the complexity of polydrug exposures.
