Postmortem analysis of three methoxyacetylfentanyl-related deaths in Denmark and in vitro metabolite profiling in pooled human hepatocytes

TY - JOUR

T1 - Postmortem analysis of three methoxyacetylfentanyl-related deaths in Denmark and in vitro metabolite profiling in pooled human hepatocytes

AU - Mardal, Marie

AU - Johansen, Sys Stybe

AU - Davidsen, Anders Bork

AU - Telving, Rasmus

AU - Jornil, Jakob R

AU - Dalsgaard, Petur Weihe

AU - Hasselstrøm, Jørgen B

AU - Øiestad, Åse M

AU - Linnet, Kristian

AU - Andreasen, Mette F

PY - 2018/9

Y1 - 2018/9

N2 - Methoxyacetylfentanyl belongs to the group of fentanyl analogues and has been associated with several deaths in recent years. We present three case reports of deceased individuals that tested positive for methoxyacetylfentanyl consumption, as well as in vitro and in vivo metabolite profiles.Methoxyacetylfentanyl was quantified by ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) in femoral blood, as well as in urine and brain tissue when these were available. Metabolite profiling was performed by incubating methoxyacetylfentanyl with pooled human hepatocytes (pHH) in Leibovitz's L-15 medium supplemented with fetal bovine serum. Metabolites were identified in vivo and in vitro using UHPLC–high resolution (HR)–MS/MS.The measured methoxyacetylfentanyl concentration was 0.022–0.056 mg/kg (N = 3) in femoral blood, 0.12 mg/kg (N = 1) in urine, and 0.074 mg/kg (N = 1) in brain tissue homogenate. A total of 10 metabolites were identified. The observed metabolic pathways were: hydroxylation(s), N-dealkylation, O-demethylation, deamination, glucuronidation, and combinations thereof. Major analytical targets in vitro and across measured biological samples in vivo were methoxyacetylfentanyl, the O-demethyl- metabolite, and the deamide-metabolite. Intoxication with methoxyacetylfentanyl was judged as the cause of death or a major contributing factor in all three presented cases.

AB - Methoxyacetylfentanyl belongs to the group of fentanyl analogues and has been associated with several deaths in recent years. We present three case reports of deceased individuals that tested positive for methoxyacetylfentanyl consumption, as well as in vitro and in vivo metabolite profiles.Methoxyacetylfentanyl was quantified by ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) in femoral blood, as well as in urine and brain tissue when these were available. Metabolite profiling was performed by incubating methoxyacetylfentanyl with pooled human hepatocytes (pHH) in Leibovitz's L-15 medium supplemented with fetal bovine serum. Metabolites were identified in vivo and in vitro using UHPLC–high resolution (HR)–MS/MS.The measured methoxyacetylfentanyl concentration was 0.022–0.056 mg/kg (N = 3) in femoral blood, 0.12 mg/kg (N = 1) in urine, and 0.074 mg/kg (N = 1) in brain tissue homogenate. A total of 10 metabolites were identified. The observed metabolic pathways were: hydroxylation(s), N-dealkylation, O-demethylation, deamination, glucuronidation, and combinations thereof. Major analytical targets in vitro and across measured biological samples in vivo were methoxyacetylfentanyl, the O-demethyl- metabolite, and the deamide-metabolite. Intoxication with methoxyacetylfentanyl was judged as the cause of death or a major contributing factor in all three presented cases.

U2 - 10.1016/j.forsciint.2018.07.020

DO - 10.1016/j.forsciint.2018.07.020

M3 - Journal article

C2 - 30107329

SN - 0379-0738

VL - 290

SP - 310

EP - 317

JO - Forensic Science International

JF - Forensic Science International

ER -