Evidence of Designer Benzodiazepine Use in Routine Healthcare Urine Drug Specimens

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.

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.

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.

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.