Background: The veterinary sedative xylazine has been mostly described on the East Coast-yet early reports indicate that it is now arriving to West Coast fentanyl markets. Emerging drug checking approaches can provide information about the concentration and prevalence of xylazine in illicit fentanyl. Methods: Fentanyl samples from a community-based drug checking program in Los Angeles, California were assessed using direct analysis in real time mass spectrometry (DART-MS). A subset was analyzed with liquid chromatography gas spectrometry (LC-MS) to quantify the concentration of xylazine, fentanyl, and other compounds. Results: Among n=536 fentanyl-positive samples, xylazine positivity rose from 0% in 2023 Q1 to a peak of 29.5% in 2025 Q1. A significant time trend was observed (OR per quarter year= 1.35 [95%CI: 1.19-1.52]). Xylazine concentration in fentanyl samples was generally low, with a highly skewed distribution (mean=2.42%, sd=7.80%). 76.9% of xylazine-positive samples had <1.0% xylazine concentration. Compared to xylazine-negative samples, xylazine-positive samples were more likely to contain BTMPS (46.60% vs 17.30%), and lidocaine (65.0% vs 29.6%), and had lower average fentanyl concentration (6.12% vs 10.7%). Conclusions: Among illicit fentanyl samples in LA, we note increasing xylazine positivity. The distribution of xylazine concentration is highly skewed, with a small number of very high concentration samples, and majority with <1%. Nevertheless, more research is needed to study the health impacts of even the low concentration xylazine that is most predominant here; given that the average participant in our sample consumes about 1.0g of illicit fentanyl daily, the corresponding dose of 24mg of xylazine per day may be physiologically significant.

The authors have declared no competing interest.

The authors report no conflicts of interest. JRF received funding from the National Institute on Drug Abuse (DA049644) and the National institute of Mental Health (MH101072). CLS received support from the National Institute on Drug Abuse (K01DA050771). AJK received educational support from the NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI (TL1TR001883). This work was supported by the Centers for Disease Control and Prevention as part of Overdose Data to Action: LOCAL (CDC-RFA-CE-23-0003), and made possible through an equipment grant from the James B. Pendleton Charitable Trust to the UCLA AIDS Institute and UCLA Center for AIDS Research. The funders played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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