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Background: The increasing prevalence of xylazine in the illicit drug supply is a growing concern for major health consequences in individuals who use fentanyl mixed with xylazine, but limited data are available regarding the pharmacokinetics of xylazine in humans., Methods: Xylazine was quantified in serial remnant plasmas collected from 28 patients starting at the initial patient encounter and continuing for up to 52 h from presentation, using LC-MS/MS to calculate the terminal half-life for xylazine. Xylazine metabolites were identified by product ion scanning, and multiple reaction monitoring was used to estimate the relative abundance of xylazine metabolites in 74 collected plasma samples., Results: The median terminal half-life for xylazine was calculated to be 12.0 h (range: 5.9-20.8). Oxo-xylazine and sulfone-xylazine metabolites were detected in all plasma specimens that contained xylazine., Conclusions: The half-life of xylazine in humans is longer than previously observed in animal studies, which furthers the current understanding of the expected duration of effects in individuals who use fentanyl mixed with xylazine and the window of detection. Both oxo-xylazine and sulfone-xylazine appear to circulate in plasma for as long as xylazine., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Free triiodothyronine (fT3) testing is most useful when thyroid stimulating hormone (TSH) is suppressed, and free thyroxine (fT4) is normal or decreased. These laboratory values in a symptomatic patient are referred to as T3 thyrotoxicosis. Standards for fT3 reflex testing have not been established. Herein, we examined the clinical utility of fT3 with the goal of identifying a TSH cutoff in the context of normal/decreased fT4 that maximizes the utility of measuring fT3., Methods: TSH, fT4, and fT3 results between January 2016 and October 2021 were extracted from the laboratory information system and grouped if resulted on the same day for the same patient. Frequency of biochemical T3 thyrotoxicosis was evaluated at different TSH cutoffs and in outpatient vs inpatient settings., Results: Of the 4366 TSH-fT4-fT3 results, 70 (1.6%) were consistent with biochemical T3 thyrotoxicosis. The common reasons were previously diagnosed hyperthyroidism on antithyroid medication (n = 28) or hypothyroidism on thyroid medication (n = 18) and newly diagnosed hyperthyroidism (n = 20, 0.5%). The likelihood of detecting T3 thyrotoxicosis increased with lower TSH cutoff (<0.3 μIU/mL, 10.3% vs <0.0 1μIU/mL, 27.6%). All patients with newly diagnosed hyperthyroidism had TSH <0.01 μIU/mL. Higher frequency of T3 thyrotoxicosis was observed in the outpatient setting (34%) relative to the inpatient setting (14%, P < 0.001) when TSH < 0.01 μIU/mL., Conclusions: T3 thyrotoxicosis is a relatively rare diagnosis and fT3 measurement has limited utility in the vast majority of patients. A fT3 reflex for patients with TSH <0.01 μIU/mL and normal/low fT4 may improve clinical utility and reduce unnecessary testing, especially in the outpatient setting., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)