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

Abstract

Purpose: Development 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. Methods: Biological 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. Results: The 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. Conclusions: The 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.