Detection of fentanyl and fentanyl analogues in biological samples using liquid chromatography-high resolution mass spectrometry.

BACKGROUND: Fentanyl and analogues such as butyrylfentanyl, carfentanil, 4-fluorobutyrylfentanyl, and furanylfentanyl may be either added to, or sold as, heroin. Fentanyl and carfentanil have approximately 100 and 10,000 times the potency of morphine, respectively, and there is thus a high risk of death with the use of these drugs. METHODS: We looked for fentanyl/fentanyl analogues using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in selected biological samples obtained post-mortem February 2017-end January 2018. Suspicion of fentanyl poisoning arose from the circumstances of death, a history of heroin use, and the geographical area in which the deceased was discovered, supplemented by drugs intelligence data. RESULTS: Of the 84 deaths investigated, fentanyl and/or a fentanyl analogue were detected in 40 (48%). The fentanyls encountered were carfentanil (N = 17), fentanyl (9), carfentanil and fentanyl together (12), and fentanyl, carfentanil, 4-fluorobutyrylfentanyl, and butyrylfentanyl together (2). The median (range) post-mortem blood fentanyl concentration was 2.66 (0.21-107) µg/L and the median (range) carfentanil concentration was 0.24 (0.03-1.66) µg/L. The most prevalent compounds present together with fentanyls were ethanol [N = 28, median (range) post-mortem blood concentration: 44 (<10-249) mg/dL)], benzoylecgonine [N = 22, 0.64 (<0.05-3.17) mg/L] and free morphine [N = 20, 0.05 (<0.05-0.34) mg/L]. Deaths in hospital excluded, median blood free morphine, and ethanol concentrations were significantly lower in deaths where fentanyl/fentanyl analogues were present, but there was much overlap with the blood concentrations of these analytes in the non-fentanyl related deaths. A routine drugs of abuse assay using LC-HRMS identified fentanyl with 100% sensitivity and carfentanil with 89% sensitivity. CONCLUSIONS: Given their potency, misuse of fentanyl and its analogues is likely to cause severe toxicity. A simple LC-HRMS method detected all cases in which fentanyl was identified post-mortem and most of the cases in which carfentanil was detected.