Abstract
Carfentanil, one of the most potent opioids known, has recently been reported as a contaminant in street heroin in the United States and Europe, and is associated with an increased number of life-threatening emergency department admissions and deaths. Here, we report on the application of a novel in vitro opioid activity reporter assay and a sensitive bioanalytical assay in the context of a fatal carfentanil intoxication, revealing the highest carfentanil concentrations reported until now. A 21-year-old male was found dead at home with a note stating that he had taken carfentanil with suicidal intentions. A foil bag and plastic bag labeled “C.50” were found at the scene. These bags were similar to a sample obtained by the Belgian Early Warning System on Drugs from a German darknet shop and to those found in the context of a fatality in Norway. Blood, urine and vitreous, obtained during autopsy, were screened with a newly developed in vitro opioid activity reporter assay able to detect compounds based on their μ-opioid receptor activity rather than their chemical structure. All extracts showed strong opioid activity. Results were confirmed by a bioanalytical assay, which revealed extremely high concentrations for carfentanil and norcarfentanil. It should be noted that carfentanil concentrations are typically in pg/mL, but here they were 92 ng/mL in blood, 2.8 ng/mL in urine, and 23 ng/mL in vitreous. The blood and vitreous contained 0.532 and 0.300 ng/mL norcarfentanil, respectively. No norcarfentanil was detected in urine. This is the first report where a novel activity-based opioid screening assay was successfully deployed in a forensic case. Confirmation and quantification using a validated bioanalytical procedure revealed the, to our knowledge, highest carfentanil concentrations reported in humans so far.
Highlights
Carfentanil, a very potent derivative of the pharmaceutical opioid fentanyl, was developed in 1974 by Janssen Pharmaceutica (Van Bever et al, 1976)
Application of carfentanil and fentanyl solutions on the opioid activity reporter assay resulted in concentration-dependent curves and EC50 (95% confidence interval profile likelihood) values were determined for carfentanil [EC50 = 0.027 nM (0.021–0.035)] and fentanyl [EC50 = 4.32 nM (2.43–7.83)] as a measure of relative potency (Figure 2A)
Given the continued emergence of novel synthetic opioids, the major disadvantage for their detection via immunoassays, GC– MS and LC–MS/MS analysis is that the methods are often targeted in nature or, for the latter two, limited by the availability of pre-established mass spectral libraries
Summary
Carfentanil, a very potent derivative of the pharmaceutical opioid fentanyl, was developed in 1974 by Janssen Pharmaceutica (Van Bever et al, 1976). We report on the application of a novel cell-based bioassay and a sensitive bioanalytical assay in the context of a fatal carfentanil intoxication, in which we found the highest carfentanil concentrations reported until now. An additional opioid screening of the biological matrices was done with a new in-house developed opioid activity reporter assay.
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