Deaths due to opioid overdoses have been on the rise in the United States, with a particular spike in this trend caused by the emergence of synthetic opioids including fentanyl and analogues. There have been numerous reported cases of synthetic opioids as adulterants in heroin, methamphetamine, cocaine, and counterfeit pills. As a result, they are often times consumed unknowingly, causing mixed toxidromes and confounding diagnosis. Proper routine drug monitoring is essential in addressing the ever-expanding magnitude of the opioid epidemic.
The primary objective of this study was to observe prevalence of fentanyl analogs and other false positives in positive fentanyl screens of emergency medicine populations in order to evaluate trends in the dynamic landscape of substance abuse.
Analysis of remnant clinical samples was approved by the UCSF Institutional Review Board. Urine samples from emergency department (ED) patients with drugs-of-abuse screens performed were monitored from October 2018 to March 2019 for presence of fentanyl (via immunoassay). Samples with a positive fentanyl screen were collected and further characterized by high resolution mass spectrometry (LC-HRMS). Urine samples were diluted 1:5. Chromatography was performed using a Kinetex C18 column with a 10-minute gradient from 2%-100% organic. Data was collected on a SCIEX TripleTOF®5600 using a positive-ion mode TOF-MS survey scan with IDA-triggered collection of high resolution product ion spectra (20 dependent scans). Data was screened for fentanyl, norfentanyl, 13 literature-reported synthetic opioids, and compounds reported/suspected to cause false positives with fentanyl immunoassays.
158 emergency department patient samples screened positive via EMIT fentanyl immunoassay (7.44% of all ED samples screened for drugs of abuse). These samples were analyzed via LC-HRMS and analysis was targeted for 15 synthetic opioids and commonly prescribed or over-the-counter pharmaceuticals with chemical structures similar to that of fentanyl. 6.9% of samples were found to be positive for both fentanyl and acetyl fentanyl. Additionally, risperidone, its metabolite 9-hydroxyrisperidone (paliperidone), and loperamide with its metabolite desmethylloperamide were discovered as sources of false positive for fentanyl screens.
This data reveals the non-trivial prevalence of fentanyl in the ED patient population being screened for drugs of abuse. In many of the cases, fentanyl was not suspected or discovered as exposure agent prior to more comprehensive testing or patient discharge. The identification of acetyl fentanyl along with fentanyl via HRMS analysis can hint to a changing trend in provenance of illicitly manufactured fentanyl. Finally, HRMS is a valuable tool to identify compounds responsible for reoccurring false positives that can inform better patient care and offer a more accurate picture of the continually evolving opioid epidemic.