Prevalence of novel psychoactive substances in selected clinical urine specimens submitted for drug monitoring

Novel psychoactive substances (NPS) are compounds emerging as alternatives to more established drugs of abuse. They are constantly changing and being modified, which makes their detection difficult. The study objective was to determine the prevalence of NPS in selected clinical specimens. Deidentified urine specimen remnants were analyzed that had previously been submitted for testing from six different regions in the United States and representing three different clinical categories: specimens submitted for smaller legacy LC-MS/MS NPS panels (ie, NPS-targeted, negative test results), immunoassay-positive but LC-MS/MS-negative traditional benzodiazepine and opiate specimens, and fentanyl/norfentanyl LC-MS/MS-positive specimens. A new, validated, large-panel LC-MS/MS method analyzed for 88 NPS including designer fentanyl analogs, designer benzodiazepines, designer opioids, designer stimulants and hallucinogens, synthetic cannabinoids, and other additives (e.g., xylazine). In total, 3753 deidentified remnant specimens were analyzed between March and July 2023 with 13.3% of specimens testing positive for ≥1 NPS, with 30 different NPS detected; most of which were from the Eastern part of the United States. Xylazine was the most prevalent NPS and was detected in all regions and specimen categories, but the other analytes were not consistently observed across the six regions. In terms of specimen remnant categories, NPS positivity was 5.5% for the NPS-targeted specimens, 10.7% for opiate/benzodiazepine specimens, and 43.7% for fentanyl/norfentanyl specimens. Our data demonstrate variability in the NPS landscape and that testing for NPS in clinical urine specimens can help give clinicians a better awareness of drug misuse among their patients.