Xylazine, an approved animal tranquilizer in the U.S., acts as a sedative and analgesic for veterinary use [1]. It is an α-2 adrenoreceptor agonist, detected in the unregulated drug supply throughout the eastern United States and Canada [2]. It has been detected in 91% of fentanyl/ heroin samples in Philadelphia and showed its presence in national overdose deaths, five times higher in 2020 than in 2015 [3, 4]. The Drug Enforcement Administration (DEA) Laboratory System has reported that approximately 23% of fentanyl powder and 7% of fentanyl pills contain xylazine. The drug users who take a mixture of xylazine and fentanyl are at higher risk of fatal drug poisoning. Moreover, injecting xylazine containing drug mixtures can result in developing severe wounds including necrosis [5]. Another study has reported that about 78% of people in Philadelphia who screened positive for fentanyl also showed positive results for xylazine [6].
Xylazine functions similar to clonidine, a medication used to treat hypertension or opioid withdrawal. It causes a decrease in the release of dopamine and norepinephrine in the central nervous system and acts as a vasoconstrictor. These can lead to muscle relaxation, sedation, hypotension, respiratory depression, bradycardia, and reduced response to painful stimuli [7]. The Federal Drug Administration (FDA) has authorized xylazine as a tranquilizer only for veterinary use [8]. In 2008, the Philadelphia Medical Examiner’s office was the first to report the association of xylazine in drug related deaths in Philadelphia [9]. Recently, it has been reported that xylazine is continuously present in the local drug supply [10]. Moreover, analytical reports showed 100% prevalence of fentanyl cut with xylazine in all tested drug samples [11]. In 2019, 31% of fatal fentanyl and heroin cases also involved xylazine exposure, reported the Philadelphia Department of Public Health [12].
In humans, the lethal dose (LD50) for xylazine has not been established. However, 14 mg/kg for intramuscular injection has been cited as a low toxic dose (TDLo) [13]. The plasma half-life for xylazine through intramuscular injection was estimated to be 4.9 hrs. The maximum concentration of xylazine was 4.6 mg/L in plasma and 194 μg/ml in urine [14]. The LC-MS/MS method has been reported as the most suitable method for detecting xylazine in urine. Recent results from different toxicology labs using LCMS/MS testing suggest a high prevalence of xylazine in fentanyl positive samples. In drugs of abuse testing, it has been reported that the LC-MS/MS assay detected a high prevalence of xylazine (>10 ng/ml) presence among fentanyl positive urine samples.
LC-MS/MS is the most advanced drug testing technology due to its precision, accuracy, and sensitivity. Jant Pharmacal offers the LCMS method for xylazine which can be included in a customized LCMS panel. For a list of available analytes that can be used in your custom panel please visit
References
1] S.A. Greene, J.C. Thurmon, Xylazine–a review of its pharmacology and use in veterinary medicine, J. Vet. Pharmacol. Ther. 11 (4) (1988) 295–313, https://doi. org/10.1111/j.1365-2885.1988.tb00189.x
2] Bowles, J.M., McDonald, K., Maghsoudi, N., Thompson, H., Stefan, C., Beriault, D.R., Werb, D., 2021. Xylazine detected in unregulated opioids and drug administration equipment in Toronto, Canada: clinical and social implications. Harm Reduct. J. 18 (1), 1–6. doi: 10.1186/S12954-021-00546-9/TABLES/2.
3] Friedman, J., Montero, F., Bourgois, P., Wahbi, R., Dye, D., Goodman-Meza, D., Shover, C., 2022. Xylazine spreads across the US: a growing component of the increasingly synthetic and polysubstance overdose crisis. Drug Alcohol Depend. 233, 109380. doi: 10.1016/J.DRUGALCDEP.2022.109380.
4] Philadelphia Department of Public Health. (2022). Health alert risks of Xylazine use and withdrawal in people who use drugs in Philadelphia.
5] https://www.dea.gov/alert/dea-reports-widespread-threat-fentanyl-mixed-xylazine.
6] Korn, W.R., Stone, M.D., Haviland, K.L., Toohey, J.M., Stickle, D.F., 2021. High preva-lence of xylazine among fentanyl screen-positive urines from hospitalized patients, Philadelphia, 2021. Clin. Chim. Acta 521, 151–154. doi: 10.1016/J.CCA.2021.07.010
7] Shi, X.X., Yin, B.S., Yang, P., Chen, H., Li, X., Su, L.X., Wang, H.B., 2016. Xylazine activates adenosine monophosphate-activated protein kinase pathway in the central nervous system of rats. PLoS One (4) 11. doi: 10.1371/JOURNAL.PONE.0153169
8] Mohr, A., Browne, T., Martin, D., & Logan, B. (2020). Xylazine: a toxic adulter-ant found in illicit street drugs. Retrieved from https://www.nvopioidresponse.org/wp-content/uploads/2020/10/u-public-alert-xylazine-003.pdf
9] S.C. Wong, J.A. Curtis, W.E. Wingert, Concurrent detection of heroin, fentanyl, and xylazine in seven drug-related deaths reported from the Philadelphia Medical Examiner’s Office, J. Forensic Sci. 53 (2) (2008) 495–498, https://doi.org/ 10.1111/j.1556-4029.2007.00648.x
10] A.L.A. Mohr, T. Browne, D.M. Martin, B.K. Logan, Xylazine: A Toxic Adulterant Found in Illicit Street Drugs. Center for Forensic Science Research and Education (CFSRE). (2020). URL: https://www.npsdiscovery.org/xylazine-a-toxic-adultrant-found-in-illicit-street-drugs/
11] A.J. Krotulski, J. Shinefeld, K. Viner, B.K. Logan, Drug Supply Assessment (Q1 2021): Philadelphia, Pennsylvania, USA, Center for Forensic Science Research and Education (CFSRE). (2021). URL: https://www.npsdiscovery.org/drug-supply-assessment-q1-2021-philadelphia-pennsylvania-usa/
12] J. Johnson, L. Pizzicato, C. Johnson, K. Viner, Increasing presence of xylazine in heroin and/or fentanyl deaths, Philadelphia, Pennsylvania, 2010-2019, Inj. Prev. (2021), https://doi.org/10.1136/injuryprev-2020-043968
13] S.G. Carruthers, M. Nelson, H.R. Wexler, C.R. Stiller, Xylazine hydrochloridine (Rompun) overdose in man, Clin. Toxicol. 15 (3) (1979) 281–285, https://doi.org/ 10.3109/15563657908989878
14] U. Hoffmann, C.M. Meister, K. Golle, M. Zschiesche, Severe intoxication with the veterinary tranquilizer xylazine in humans, J. Anal. Toxicol. 25 (2001) 245–249, https://doi.org/10.1093/jat/25.4.245
