Widespread Distribution of Xylazine Detected Throughout the United States in Healthcare Patient Samples.

OBJECTIVES: Xylazine is a tranquilizer commonly added into the illicit drug supply and a likely contributor to overdoses because it does not respond to naloxone reversal. The objective of this study was to perform a retrospective data analysis on xylazine-positive samples collected from patients in various outpatient healthcare settings to illustrate geographic distribution and common copositive substances, which may also contribute to risk of adverse events. METHODS: Samples for which providers ordered testing for xylazine were subjected to enzymatic hydrolysis, extracted, and analyzed using liquid chromatography-tandem mass spectrometry. Retrospective analysis was performed on xylazine-positive samples collected from April 2021 to March 2022, to include geographic location and copositive substances. RESULTS: Xylazine was identified in 413 of 59,498 samples from adults aged 20-73 years and originated from 25 of the 39 states where xylazine testing was ordered. The most common routine substances detected with xylazine were fentanyl, buprenorphine, naloxone, cocaine, d -methamphetamine, and delta-9-tetrahydrocannabinol. The most common designer drugs detected included fentanyl analogs, isotonitazene, and designer benzodiazepines. CONCLUSIONS: Xylazine is geographically spread throughout the United States, indicative of a wide incorporation into the illicit drug supply. These findings differ from previous studies in that these samples originated from healthcare providers in routine care settings, where other reports typically involve overdose deaths. This analysis illustrates that routine testing for xylazine in outpatient settings can afford providers the opportunity to educate individuals and adjust harm reduction measures to potentially mitigate overdose risk.

Evidence of Designer Benzodiazepine Use in Routine Healthcare Urine Drug Specimens.

OBJECTIVES: The illicit drug market continuously evolves, with new substances introduced to mimic prescription or other illicit drugs while evading detection by routine drug testing. The objective was to determine if designer benzodiazepines would be present in urine samples collected from patients in various healthcare settings. METHODS: Samples for which providers ordered testing for prescription benzodiazepines during the study period were diluted, subjected to enzymatic hydrolysis, and analyzed using liquid chromatography- tandem mass spectrometry. In addition to prescription benzodiazepines, samples were also analyzed for presence of any of the following designer benzodiazepines: etizolam, diclazepam, delorazepam, lormetazepam, flubromazepam, flubromazolam, and phenazepam. RESULTS: Of 38,073 samples tested, 40 samples contained a designer benzodiazepine and/or a metabolite. Of the 40 samples, 19 (47.5%) also tested positive for a prescription benzodiazepine. Twenty-one samples (52.5%) did not test positive for a prescription benzodiazepine, which would result in undetected benzodiazepine use had only traditional definitive testing methods been employed. Thirty-three (82.5%) samples contained an opioid, including 22 (55%) positive for buprenorphine and/or methadone. CONCLUSIONS: The potential harms from the use of designer benzodiazepines are widely unknown due to the lack of traditional pharmacokinetic studies and good manufacturing processes. Our analysis shows that when a designer benzodiazepine was present, over 80% of samples also contained an opioid or a prescription benzodiazepine, which may increase the risk of a drug interaction or adverse drug event. Providers may benefit from knowledge of their patients' designer benzodiazepine use when formulating risk mitigation strategies as part of a treatment plan.