Abstract Introduction: The opioid crisis continues to grow resulting in a large number of fatal and nonfatal overdoses each year in the United States. Increasing use of fentanyl and related analogs poses a significant risk of fatal overdose due to their high potency and unpredictable pharmacokinetics. Fentanyl is a synthetic opioid primarily prescribed for pain management and anesthesia procedures but is also produced and used illegally, often mixed with other drugs such as heroin, xylazine, methamphetamine and cocaine. The combination of fentanyl with other psychoactive substances can be highly toxic. As part of the South Carolina (SC) statewide response to the opioid crisis, the SC Public Health Laboratory (PHL) tested specimens for fentanyl and fentanyl analogs from suspected opioid-related emergency department visits from across the state.
Objectives: To monitor exposure to opioids, particularly fentanyl and fentanyl related analogs, and other psychoactive substances for timely information on emerging drug trends for opioid biosurveillance across the state to effectively combat the opioid crisis.
Methods: Residual de-identified urine specimens from overdose patients were analyzed for fentanyl related analogs using liquid chromatography high resolution mass spectrometry. Analysis was performed on an Exion ultra high-performance liquid chromatograph (UHPLC) system coupled to a SCIEX X500R Quadrupole Time of Flight Mass Spectrometer (QTOF). The method was validated to include 21 analytes in the quality control solutions and the limit of detection varied from 0.5 ppb to 7 ppb. The analytes include: Fentanyl, Carfentanil, 3-Methyl fentanyl, Acryl fentanyl, Valeryl fentanyl, Cyclopropyl fentanyl, Furanyl fentanyl, para-Fluorobutyryl fentanyl, Butyryl fentanyl, para-Fluoro fentanyl, β-Hydroxythio fentanyl, Acetyl fentanyl, U-47700, U-48800, U-49900 and 4-ANPP, Methoxyacetyl fentanyl, Remifentanyl, Norfentanyl, Norcarfentanyl and Naloxone. We are building our in-house library to expand the testing to 200+ synthetic opioids, the majority of which are fentanyl analogs, and other drugs of abuse.
Results: The SC Public Health laboratory has analyzed over 5000 residual urine samples for suspected opioid overdoses since 2020. Of these, approximately 25% tested positive for fentanyl or fentanyl analogs. The most common detected analytes were Fentanyl, Norfentanyl and 4-ANPP. Other analytes that tested positive in the submitted specimens include, para-Fluorofentanyl, Acetyl Fentanyl, para-Fluorobutyryl fentanyl, Valeryl fentanyl, Butyryl fentanyl, Acryl Fentanyl, 3-Methyl Fentanyl, β-Hydroxythiofentanyl, Furanyl fentanyl, Carfentanil, U-47700 and U-48800.
Conclusion: Screening of suspected opioid overdose samples using high resolution mass spectrometry allows the lab to identify novel fentanyl analogs and emerging drug trends within affected communities. Early identification of drug trends among non-fatal overdoses can be useful in preventing fatal overdoses by providing useful information for harm reduction strategies. Specimens from opioid-related emergency department visits from hospitals around the state have resulted in an expansion of the biosurveillance of opioid usage in a broader segment of the SC population.
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