Quantification and distribution of 4-fluoroisobutyryl fentanyl (4-FiBF) in postmortem biological samples using UHPLC\u2013QqQ-MS/MS

Abstract

PurposeDevelopment of ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry method for quantification of 4-fluoroisobutyryl fentanyl (4-FiBF) and its distribution in postmortem biological samples in four fatal intoxication cases, which occurred in September 2018, in Poland.MethodsBiological fluids (blood, urine, vitreous humor, bile, gastric content) and tissues (brain, kidney, liver, stomach wall) were extracted with ethyl acetate from alkaline medium (pH 9). Fentanyl-d5 was used as internal standard.ResultsThe validation parameters were as follows: lower limit of quantification: 0.1 ng/mL (biological fluids) and 0.1 ng/g (solid tissues), intra- and inter-day accuracies and precisions: not greater than 20%; recovery values: 86.9–110%; matrix effect: − 13.1–10.4%. Among all tested biological fluid, the highest concentration of 4-FiBF was found in bile (average concentration of 3390 ng/mL) while among the tissues, in liver (average concentration of 1650 ng/g). Furthermore, in collected specimens, there were also found other drugs and new psychoactive substances (NPS) e.g. N-ethylpentylon, 4-chloromethcathinone (4-CMC) and α-pyrrolidinoisohexanophenone (α-PiHP). Concentrations and distributions of these substances in postmortem samples have been also detailed. Examinations of seized drug (in case 4) revealed that it included the mix of 4-FiBF and α-PiHP.ConclusionsThe developed and fully validated method enabled for determination of 4-FiBF in postmortem biological fluids and tissues. To our knowledge, this is the first report of distribution study of 4-FiBF with other NPS (N-ethylpentylon, 4-CMC and α-PiHP) in authentic fatal intoxication cases.