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

ABSTRACT

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.

1. Introduction and background

Xylazine and medetomidine are non-opioid, α2-adrenergic agonists commonly used in veterinary medicine for the sedation of animals, but neither is approved for use in humans. Xylazine was initially developed as an antihypertensive agent, but adverse effects, including profound hypotension, led to the abandonment of its development for human use. In veterinary medicine, medetomidine is known to be significantly more potent than xylazine due to greater α2-adrenergic receptor affinity [1,2]. Despite not being approved for human use, xylazine, and more recently medetomidine, are being detected with increasing prevalence in illicit drug supplies, and in the urine and blood of persons who use drugs, and overdose victims [3–7].

The adulteration of illicit drug supplies with xylazine was first recognized and reported in Puerto Rico and Philadelphia starting around 2008 [8,9]. Between 2010 and 2015, surveillance sites in Philadelphia detected xylazine in 2% of overdose death cases involving heroin and/or illicitly manufactured fentanyl (IMF), but by 2019, xylazine was detected in 31% of cases, and increasingly found in combination with IMF [10]. According to one study across 20 states and Washington D.C., the percentage of deaths involving IMF with xylazine detected increased from 3% in January 2019 to 11% in June 2022 [11]. Nearly half of the deaths with xylazine detected were identified in the Northeastern jurisdictions, and only 1% were identified in Western jurisdictions [11]. More recent reports in California show a rapid increase in xylazine prevalence among fentanyl drug samples in the West, from 0% in 2023 to 29.5% in 2025 [12]. Globally, xylazine mixed with IMF appears to be primarily found in the US and Canada, but in 2022, the first case was reported in the United Kingdom, and recent evidence suggests an increasing prevalence of xylazine in Europe [13–15].

Reports on the detection of medetomidine in biospecimens and drug supplies have emerged much more recently. In July 2022, the first identification of medetomidine in illicit drug packaging was reported in Maryland [16]. Medetomidine occurs in two enantiomeric forms: dexmedetomidine and levomedetomidine. Dexmedetomidine is approved for human medical use in procedural or general sedation, but racemic medetomidine (which includes the less active levomedetomidine enantiomer) is only approved for veterinary use [17].

In May 2024, 38 confirmed or probable cases of medetomidine-involved overdose were reported in Chicago, with patients experiencing hypertension, bradycardia, and most showing no improvement in symptoms with naloxone administration [18]. Medetomidine most frequently co-occurs with IMF (and sometimes xylazine) but has also been detected in the absence of these drugs [3,4,16,19]. The geographical prevalence of medetomidine in the illicit drug supply appears to coincide with areas where xylazine is more prevalent. The prevalence of both medetomidine and xylazine is likely underestimated overall due to limited awareness and availability of testing for these drugs [7].

Both xylazine and medetomidine bind to alpha-2 adrenergic receptors and inhibit the release of norepinephrine, leading to profound sedation and analgesia. Addition of these adulterants to IMF may be intended to prolong or enhance the euphoric effects of IMF, but they can also cause central nervous system depression, hypotension, and bradycardia [20]. Both drugs pose a risk for individuals exposed to IMF since naloxone, an opioid antidote, does not reverse their effects. There are known antidotes for these drugs in veterinary medicine, but no approved antidotes in humans [21]. Acute overdose treatment primarily focuses on addressing sedative and cardiovascular effects, including supportive airway management [21,22]. Repeated exposure to xylazine has also been linked to severe skin ulcerations that have the potential to progress to bone involvement and amputation, and these have become recognized as a distinct clinical entity [23]. Concurrent use of xylazine and/or medetomidine with IMF potentially complicates longer term treatment but much remains unknown regarding the effects of these drugs and their potential interactions with fentanyl, or other opioids [24–26].

Recognizing the substantial public health threat posed by xylazine, the White House Office of National Drug Control Policy declared it an emerging threat in April 2023, initiating an extensive response plan to address its widespread harm [27]. Medetomidine has more recently been identified as an adulterant in IMF, but its wide availability combined with increasing reports of its detection leads to significant concerns that its prevalence will continue to increase [4,7,16,19].

The frequent detection of xylazine, and increasing detection of medetomidine, in illicit drug samples, patient specimens, and the blood of overdose victims highlights the urgent need for reliable and accurate tests for these drugs. Reliable detection and quantification of xylazine and medetomidine will help to identify intoxication and exposure, support clinical studies, guide treatment, conduct forensic investigations, and monitor drug use trends. This review examines current advances in the detection of xylazine, medetomidine, and their metabolites in biological specimens, including blood, plasma, urine, and oral fluid.

2. Elimination of xylazine and medetomidine

Knowledge of a drug’s specific elimination pathways is a prerequisite for the appropriate design of testing methods, selection of appropriate target biospecimens, and interpretation of results. A method that only detects parent drug will have poor sensitivity if a metabolite is the primary form present in the target biospecimen. If major drug metabolites exhibit longer elimination half-lives compared to parent drug, detecting these metabolites can lead to a longer window of detection after exposure. These factors must be considered during assay design and development. Figure 1 shows the structures and major metabolites of xylazine and medetomidine detected in humans.

Figure 1.

Structures of xylazine, medetomidine, and major metabolites.

3. Xylazine

Much of the current knowledge of xylazine pharmacokinetics is extrapolated from animals. Studies in rats and hepatic microsomal preparations demonstrated that xylazine undergoes extensive metabolism by hydroxylation, dealkylation, C-oxidation, S-oxidation, and glucuronidation [28,29]. Based on these studies, hydroxy-xylazine was observed as a major metabolite in animals and believed to be a major urinary metabolite in humans. Several larger and more recent studies in humans observed these metabolites at relatively low concentrations or undetectable in the urine of most individuals exposed to illicit xylazine [30–32]. Other known xylazine metabolites include 2,6-dimethylaniline and N-(2,6-dimethylphenyl) thiourea, but recent studies have not successfully detected these in individuals exposed to xylazine [3,33]. Additionally, while 2,6-dimethylaniline is a known xylazine metabolite, it is also a metabolite of lidocaine – a local anesthetic and a known adulterant in heroin/fentanyl mixtures. Therefore, 2,6-dimethylaniline cannot be reliably used as a biomarker for xylazine exposure.

Recent studies in patients exposed to fentanyl mixed with xylazine confirmed the presence of oxo-xylazine and sulfone-xylazine as major metabolites in human plasma and calculated a median plasma half-life for xylazine of 12 hours [34]. In urine, xylazine is eliminated in free form alongside the major metabolites sulfone-xylazine, and hydroxy-oxo-xylazine-glucuronide [35]. Xylazine can undergo N-glucuronidation, and hydroxy-xylazine can undergo O-glucuronidation, but these appear to be minor metabolic pathways in most individuals [31,32].

4. Medetomidine

Given the clinical use of dexmedetomidine in humans for at least 25 years, knowledge of dexmedetomidine pharmacokinetics in humans has been extensively studied and can be extrapolated to medetomidine. Dexmedetomidine is rapidly distributed and extensively metabolized to inactive metabolites with a half-life of 2–3 hours in healthy adults, and this may be prolonged to 7–8 hours in individuals with severe hepatic impairment [36]. It is important to note that the existing pharmacokinetic data for dexmedetomidine were collected in clinical settings after single or short-term dosing to target concentrations around 1 ng/mL. These observations may not apply to individuals exposed to higher doses, or exposed chronically.

The majority of dexmedetomidine metabolites are excreted renally with <1% of parent drug excreted unchanged [37]. In one study, including 10 patients suspected to be exposed to medetomidine, only 2 patient urines contained detectable medetomidine but all contained medetomidine metabolites [38]. Metabolites include N-glucuronides-, N-methyl-O-glucuronide, and 3-hydroxy-medetomidine [37,39]. Less is known about the pharmacokinetics of levomedetomidine in humans but in dogs clearance of levomedetomidine is more rapid than dexmedetomidine [40]. Studies with human liver microsomes and recombinant UDP glucuronosyltransferase (UGT) also demonstrate stereospecificity in the N-glucuronidation of medetomidine [41].

5. Estimated windows of detection

Based on the observed half-life of xylazine in plasma (12 hours), a reasonable estimate for window of detection is several days after last use, but this can also be affected by assay limit of detection, dosing and mode of administration, hepatic and/or renal function, and potentially pharmacogenetic differences, and/or drug–drug interactions [34]. Particularly for xylazine, unavailability of commercial standards for major metabolites presents a challenge to their routine inclusion in clinical and/or forensic assays, and it is currently unknown whether their detection might improve the sensitivity or window of detection for exposure. The short half-life of dexmedetomidine suggests an even shorter window of detection for medetomidine, and this is consistent with the detection of medetomidine metabolites in the absence of medetomidine in urine.

Both xylazine and medetomidine are lipophilic with large volumes of distribution which could potentially result in prolonged elimination kinetics in a setting of chronic dosing. For example, in patients chronically exposed to fentanyl, the major norfentanyl metabolite may be detectable in urine for 3–4 weeks post-cessation, reflecting an elimination phase which is significantly longer than the 2–4 days that norfentanyl is generally detectable in urine after short term medical administration during clinical anesthesia [42,43].

6. Detection in blood

Knowledge of the expected concentrations of a drug and major drug metabolites in the target biospecimen is a key factor in assay design and development. A summary of reported concentrations of xylazine and medetomidine measured in poly-drug exposures with IMF, for both living patients and postmortem cases are listed in Table 1. Prior to the emergence of xylazine as an adulterant in illicit drug supplies the majority of overdoses involved individuals with occupational access to veterinary xylazine, and in the setting of single drug intoxication, the highest reported plasma xylazine concentration was 4600 ng/mL, detected in a patient that required mechanical ventilation [44]. Two more recent and independent reviews of fatal drug overdoses (occurring between 2019 and 2023, and in victims exposed to IMF mixed with xylazine) reported blood xylazine concentrations ranging from 3.3 to 2755 ng/mL [6,26]. In living patients exposed to IMF mixed with xylazine, treated for various clinical reasons and across different studies, plasma and blood xylazine concentrations ranged from <0.1 ng/mL to 127 ng/mL [3,34]. These data together demonstrate that reliable detection of xylazine exposure in blood or plasma generally requires low to sub-nanogram detection limits and analytical measurement ranges spanning several orders of magnitude. Data on major xylazine metabolites in blood and plasma is more challenging to quantify due to the unavailability of commercial standards [34].

Table 1.

Range of reported concentrations of xylazine and medetomidine in blood or plasma, urine, and oral fluid in both living patients and postmortem cases of individuals exposed to xylazine or medetomidine mixed with IMF. (n/a: not available or not applicable).

Analyte	Range of reported concentrations in living patients (ng/mL)			Range of reported concentrations in postmortem cases (ng/mL)
	Blood, Plasma	Urine	Oral fluid	Blood, Plasma	Urine	Oral fluid
Xylazine	0.1 - 127	< 1 - > 10,000	1.2 - 23.3	3.3 - 2755	n/a	n/a
Medetomidine	0.1 - 16	0.1 - 540	n/a	0.1 - 63.7	n/a	n/a

There is less data on expected blood and plasma concentrations of medetomidine in persons exposed to illicit medetomidine. Since patients may be medically administered dexmedetomidine (e.g., Precedex™), chiral analysis may help to differentiate illicit exposure from medical use in the absence of medical history. Recent studies on the chiral ratio of medetomidine in patients suggest that illicit medetomidine comes from veterinary drug sources or clandestine laboratories [3].

An analysis of biological specimens received from 14 states found medetomidine concentrations ranging from 0.1 to 32 ng/mL (median = 0.31 ng/mL) in postmortem blood, and 0.1 to 16 ng/mL (median = 1.5 ng/mL) in antemortem blood (originating from emergency department admissions) [3]. Consistent with current poly-drug exposure trends: fentanyl, xylazine, or stimulants (e.g., cocaine, methamphetamine) were co-detected alongside medetomidine in 93%, 76%, and 35% of cases, respectively. The metabolite 3-hydroxy medetomidine was rarely detected in blood of patients exposed to IMF mixed with medetomidine [3]. In a separate report on 12 cases of confirmed medetomidine-involved overdoses, blood medetomidine concentrations ranged from 0.7 to 63.7 ng/mL [18]. In this report, only the patient with the lowest reported medetomidine concentration (0.7 ng/mL) fully responded to naloxone administration, suggesting that medetomidine concentrations above this produce significant sedation. In clinical settings, target plasma concentrations for dexmedetomidine range from approximately 0.1 to 1.25 ng/mL. This range is notably more than an order of magnitude lower than the concentrations measured in recently reported overdose cases [45].

7. Detection in urine

Urine is often the biospecimen of choice for drug testing due to the ability to collect specimens without phlebotomy, the generally observed higher concentration of drugs in the urine compared to blood, and typically longer window of detection in urine compared to blood. Many drugs are excreted in the urine as metabolites and the development of sensitive urine-based assays requires an understanding of a drug’s metabolic pathways and identification of predominant urinary metabolites.

Sulfone-xylazine and hydroxy-oxo-xylazine-glucuronide have been detected in human urine with higher abundance than parent drug xylazine, but the absence of commercially available reference standards for these metabolites limits their routine detection and quantification in clinical and forensic settings [35]. Current urine-based assays primarily detect the parent drug xylazine [32,34]. Observed concentrations of xylazine in urines of individuals exposed to fentanyl mixed with xylazine span over 4-orders of magnitude, from less than 1 ng/mL to more than 10,000 ng/mL [31,35]. In our local area, in the second half of 2023, we observed that more than one-third of patients who tested positive for IMF also tested positive for xylazine, and 25% of these patients had urine xylazine concentrations between 1 and 10 ng/mL [30,35]. A recent report from New York observed a similar prevalence of xylazine positivity in patients testing positive for IMF, and most of these patients had urine xylazine concentrations below 200 ng/mL [31].

Low concentrations of xylazine in urine may reflect low overall exposure but could also be due to more distant exposure, with either scenario resulting from variations in drug supply. Analytical testing of drug samples in the Eastern US observed that the relative volume of xylazine-to-drug sample can vary from a trace amount (< 10%) to a major component (> 30%) [46]. Analytical testing of drug samples in the Western US observed that the fentanyl concentration of xylazine-positive samples was on average 43% lower than xylazine-negative samples [12]. Trends and changes in drug supplies likely affect observed biospecimen concentrations. Studies in the Midwestern US have observed steady and statistically significant increases in the relative ratio of xylazine-to-fentanyl in urine samples positive for xylazine since 2016, suggesting a change in the ratio of xylazine-to-fentanyl in illicit drug supplies over time [47].

Given the more recent emergence of medetomidine as an illicit drug adulterant, less data is available regarding expected urine concentrations in persons who use fentanyl mixed with medetomidine. The historical use of dexmedetomidine in clinical settings provides some insight into its metabolism and urinary excretion. Less than 1% of dexmedetomidine is excreted unchanged renally. Expected metabolites in urine include N-glucuronides, hydroxylated metabolites, hydroxylated-o-glucuronides, and glucuronide of the hydroxy N-methyl metabolite. Currently, only the 3-hydroxy-metabolite has a commercially available reference standard [36]. The observation of both medetomidine and 3-hydroxy-medetomidine have been recently confirmed in the urine of non-fatal overdose victims with concentrations ranging from 0.1 to 540 ng/mL for medetomidine, and 1 to 160 ng/mL for 3-hydroxy-medetomidine [3]. In this same study, 3-hydroxy medetomidine was rarely detected in blood (2%), and more frequently identified in urine (38%). A recent study in Philadelphia also identified high yield for 3-hydroxy-medetomidine metabolite after beta-glucuronidase pre-treatment and observed that 32% of the tested medetomidine exposures would have been missed without enzymatic pre-treatment, suggesting the importance of detecting 3-OH-medetomidine-glucuronide [48].

8. Detection in oral fluid

Oral fluid is another biofluid that is used for drug testing due to its ease of collection, proximity to the blood compartment, and ability to detect recent drug use. Sensitivity of oral fluid for a specific analyte varies based primarily on passive diffusion of the analyte between blood and saliva [49]. Urine generally has a longer window of detection compared to oral fluid, but oral fluid drug concentrations have better correlation to blood concentrations [50].

A recent study implemented a two-step screen-and-confirm approach to detect xylazine in oral fluid samples collected from individuals undergoing treatment for substance use disorder and identified 29 positive cases. This two-step “screen-and-confirm” approach utilized a 1 ng/mL cutoff for both screening by enzyme linked immunosorbent assay (ELISA), and confirmation by liquid chromatography tandem mass spectrometry (LC-MS/MS). Oral fluid xylazine concentrations ranged from 1.2 to 23.3 ng/mL, with a median concentration of 4.2 ng/mL [51].

9. Analytical approaches

Currently available methods to detect xylazine include immunoassays and chromatography coupled to mass spectrometry. Some of the first published methods to identify xylazine as an adulterant relied on gas chromatography mass spectrometry (GC-MS) [9]. LC-MS/MS methods have also been published, routinely achieving sub- ng/mL detection limits in blood and urine with simple extraction methods [30,52]. Detection of xylazine in urine performed by LC-MS/MS utilizing basic dilute-and-shoot preparation, demonstrates excellent sensitivity (limits of detection below 1 ng/ml), and high accuracy, with chromatographic runtimes of only a few minutes [31,35]. Similar detection limits have been reported with methods utilizing quadrupole-time-of-flight (QTOF) – an approach that enables more comprehensive screening [53–56].

Hydroxylated xylazine metabolites are excreted in the urine primarily as glucuronides and sensitive detection of these metabolites requires enzymatic pre-treatment or direct detection of glucuronides. Other abundant metabolites, such as sulfone-xylazine, as well as parent drug xylazine, are eliminated in free form with high relative abundance and do not require enzymatic pre-treatment [31,35].

Given medetomidine’s structural and chemical similarity to xylazine, it is reasonable that analytical approaches that successfully detect xylazine can be adapted to medetomidine. A recent LC-MS/MS method utilizing liquid–liquid extraction was successfully applied to simultaneously quantify medetomidine, xylazine, and selected metabolites with detection limits down to 0.1 ng/mL in blood [3]. The detection of medetomidine in urine has also been described and based on the knowledge of medetomidine metabolism, it is likely that detection of medetomidine metabolites in urine provides superior sensitivity. This includes medetomidine-n-glucuronide, and hydroxy-medetomidine-o-glucuronides.

Automated homogenous enzyme immunoassays are also available to detect xylazine in urine at concentrations as low as 10 ng/mL, although at the time of preparation of this publication, none are cleared for clinical use in the US [32]. These assays do not appreciably cross-react with medetomidine and currently there are no available commercial immunoassays for medetomidine detection. In addition to automated immunoassays, there are several lateral flow immunoassays (immunochromatographic strip-based point-of-care tests) to detect xylazine in urine. Unfortunately, the majority have detection limits that are relatively high (between 100 and 1000 ng/mL). Given that more sensitive and quantitative LC-MS/MS methods observe median urine xylazine concentrations below 100 ng/mL for the majority of patients exposed to fentanyl and xylazine, assays with these higher cutoffs will have inadequate sensitivity to reliably detect xylazine exposure [35]. The ease of use and cost effectiveness of these assays does increase the overall availability to test which means they may still contribute to increased data on the prevalence of these drugs. A recent study used lateral flow immunoassay strip tests to detect xylazine in paired drug samples and urine specimens provided by 23 participants. Urine testing provided a higher estimate of exposure compared to drug sample testing even though the urine tests had relatively high cutoffs (500 to 1000 ng/mL) [12]. Although more research is needed, this highlights the importance of drug surveillance through biospecimen testing. Drug surveillance through biospecimen testing often occurs through postmortem testing. A wider availability of testing for xylazine, medetomidine, and other novel adulterants or psychoactive substances in clinical laboratories, and/or harm reduction sites, could significantly improve surveillance efforts, and support clinical studies. Recent advances in point of care testing technology demonstrate more than an order of magnitude greater sensitivity (with detection limits as low as 10 ng/mL for xylazine) which could also lead to improved remote detection capabilities in the future [57,58]. A summary of currently reported available testing methods is provided in Table 2.

Table 2.

Summary of reported methods for xylazine and medetomidine detection. This list is not intended to be exhaustive but rather to provide a general guide.

Description of reported methods	Reference(s)
Gas-chromatography method for detection of xylazine	[9]
LC-MS/MS methods for xylazine + metabolites in urine and/or plasma	[31,34,35]
LC-QTOF methods for xylazine + metabolites in urine and/or blood	[29,52,53]
LC-MS/MS method for medetomidine + metabolites in urine and/or blood	[3,48]
ELISA and LC-MS/MS method for xylazine in oral fluid	[51]
Automated Immunoassay for xylazine in urine	[32]
Rapid lateral flow device for xylazine in urine	[58]

Although analytical drug composition analysis falls outside the scope of this review, novel methods currently used for drug composition analysis may be extended to testing of biospecimens in the future. One of the challenges of mass spectrometry-based screening is the utilization of liquid chromatography, which is time consuming and technically challenging. Thermal desorption direct analysis in real-time mass spectrometry (DART-MS) has been used for rapid and sensitive analysis of illicit drug samples, providing near-complete chemical profiles [16,59]. Recently, similar approaches have also been applied to detect novel psychoactive substances, benzodiazepines, and opioids, in urine and blood [60–62]. Advances in chromatography-free, ambient ionization technologies in the future could significantly simplify comprehensive mass spectrometry-based screening for a wide variety of drugs in urine, blood and/or oral fluid [63].

10. Discussion and summary

Xylazine continues to be a prevalent illicit drug adulterant associated with IMF. Although research is ongoing, emerging evidence suggests that the clinical manifestations and associated morbidities in individuals using fentanyl adulterated with xylazine differ significantly from those observed with fentanyl use alone [23,25,26,44]. Just as the knowledge of and ability to detect xylazine exposure is increasing, a new and related adulterant, medetomidine, is emerging with increasing prevalence. It is possible that medetomidine’s appearance in illicit drug supplies will follow a similar pattern to that observed with xylazine and experience from the threat of xylazine can inform a more rapid response to medetomidine. LC-MS/MS methods for medetomidine have been published for both blood and urine and these have enabled early observations on unique effects and treatment course for patients with suspected and confirmed medetomidine exposure [18,38,48,64]. Dexmedetomidine has been used for decades in humans (unlike xylazine, which was never approved for human use), but medetomidine blood concentrations observed after illicit exposure appear to be much higher than recommended dexmedetomidine concentrations used for clinical sedation.

Mass spectrometry-based methods will continue to lead the way for novel drug testing and poly-drug exposures. Laboratory developed methods using LC-MS/MS and LC-QTOF are possible only through the availability of standards, rapid dissemination of analytical methods and observed metabolites, and observed concentrations in various biospecimens, for newly emerging drugs. Rapidly updated resources on current illicit drug trends include the National Drug Early Warning System (NDEWS), the Center for Forensic Science Research & Education (CFSRE), local drug-checking and surveillance programs, and the Center for Disease Control and Prevention National Center for Health Statistics Provisional Drug Overdose Wonder database [65–67].

11. Conclusion

The increasing prevalence and serious health consequences of xylazine and medetomidine exposure necessitate improved detection methods for biospecimen analysis. Routine toxicology testing for xylazine and medetomidine exposure in suspected overdose cases and persons exposed to these adulterants is critical for accurate surveillance, investigation on the clinical effects of these drugs, a better understanding of their interactions with fentanyl, and the development of treatment protocols. Further investigation into xylazine and medetomidine’s effects will help guide tailored prevention and response efforts. Education for clinicians and the public, coupled with strategies to disrupt the supply of illicit xylazine and other emerging adulterants, including medetomidine, are key pillars of a comprehensive response plan [68].

12. Future perspectives

Novel drug trends have evolved dramatically over the past decade with an alarming increase in the prevalence of synthetic drugs and poly-drug mixtures. Laboratories must adapt from a traditional drug screening approach that detects a handful of drug classes to more advanced testing modalities that enable rapid evolution on par with changing illicit drug supplies. Mass spectrometry approaches, particularly those that utilize full scanning methods that allow retrospective analysis (e.g., LC-QTOF), will continue to be the most powerful tool for toxicology laboratories. These technologies will remain in specialized regional reference laboratories until they become less expensive, smaller, and easier to implement and maintain. Automated immunoassays for clinical use significantly lag drug trends but are still valuable and needed to detect frequently observed drugs. Point-of-care approaches that are inexpensive and easy to use could be a powerful tool to improve early and widespread novel drug detection, but they must have adequate sensitivity and evolve beyond single-drug assays to meet this challenge.

Article highlights

• Xylazine and medetomidine are veterinary sedatives adulterating the illicit drug supply, frequently mixed with fentanyl.

• Xylazine and medetomidine’s strong sedative effects are non-responsive to naloxone. Prolonged sedation in opioid overdose victims may suggest poly-drug exposure with xylazine and/or medetomidine.

• Methods to detect these drugs are not widely available and exposure in most cases will go undetected. These drugs can be detected by specialized laboratory developed tests.

• Immunoassays to detect xylazine are not currently approved for clinical use in the US. At the time of this publication, there are no commercially available immunoassays to detect medetomidine.

Funding Statement

The author(s) reported there is no funding associated with the work featured in this article.

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