B-304 Novel Psychoactive Substances Prevalence in Clinical Urine Specimens at Quest Diagnostics in 2024

Background Novel psychoactive substances (NPS) are known as “legal highs” and are designed to have similar effects to recreational drugs. The creators of these compounds constantly change the structures to circumvent legality issues, resulting in more than 1,000 different NPS identified since 2010. With these frequent changes, analysis of these compounds is difficult, which makes understanding what a patient may have taken illicitly even more challenging. This study aims to evaluate the prevalence of NPS detected in urine specimens and identify trends in positivity rates across different NPS categories. Methods A retrospective analysis was conducted on data from urine specimens submitted to Quest Diagnostics for NPS testing between November 2023 and December 2024. Positivity rates and trends were assessed for 88 NPS compounds in 6 categories: designer fentanyl analogs, designer benzodiazepines, designer opioids, designer stimulants, synthetic cannabinoids, and other illicit compounds. In December 2024, 25 additional analytes were added to the NPS panel. Positives seen from these analytes in December were included in the retrospective analysis. Testing was performed using a semi-quantitative method that was previously validated according to CLIA and Quest Diagnostics requirements. A 3-point calibration curve was used, and all compounds had limits of detection between 0.5 ng/mL and 10.0 ng/mL. Results In total, 8384 specimens were positive for at least 1 NPS. Most of the positive specimens (64.7%) were positive for only 1 of the 6 NPS categories; 26.2% were positive for 2 categories, 6.6% were positive for 3 categories, 2.4% were positive for 4 categories, and 0.1% were positive for 5 categories. None of the specimens were positive for all 6 NPS categories. In total, 72 different NPS were seen in various combinations in the analyzed clinical urine specimens. The most commonly detected NPS was xylazine (other illicit compounds) and was positive in 52.0% of positive specimens. The most commonly detected NPS category was other illicit compounds (52.9% of positive specimens). Designer fentanyl analogs were seen in 44.3% of positive specimens, designer benzodiazepines in 21.5% of specimens, designer opioids in 6.6% of specimens, designer stimulants in 4.0% of specimens, and synthetic cannabinoids in 17.6% of specimens. The most commonly detected designer fentanyl analogs were fluorofentanyl and acetyl fentanyl and they were always detected with fentanyl and/or norfentanyl. The most commonly detected designer benzodiazepines were bromazolam and its metabolite, hydroxy-bromazolam. The most commonly detected designer opioid metabolite was pyrrolidino hydroxy-nitazene and parent compound was metonitazene. The most commonly detected designer stimulant was dimethyl pentylone. The most commonly detected synthetic cannabinoid was the butanoic acid metabolite for MDMB-4en-PINACA. Conclusion In the specimens that were analyzed at Quest Diagnostics for NPS between November 2023 and December 2024, 8384 were positive for at least 1 NPS. Knowing which NPS a patient may have taken can help physicians develop an appropriate treatment plan; for example, designer benzodiazepines may require a different treatment plan than designer opioids. Understanding NPS prevalence in the clinical population and the variety of compounds seen in clinical specimens can help physicians understand the importance of NPS testing.