Fast & fluorinated – Development and validation of a rapid benchtop NMR approach and other routine screening methods for the detection and quantification of synthesized fluorofentanyl derivatives

Abstract

Fluorinated fentanyl regioisomers have become increasingly common in forensic casework. This study reports the synthesis of eight fluorinated fentanyl derivatives as pure reference materials and their complete NMR, infrared and mass spectral characterisation. Presumptive colour tests and TLC results are presented as an initial screening method for these compounds. The fully validated GC–MS method (employing SIM mode) allows the quantification of the target analytes (LOD = 9–20 ng/mL, LOQ = 31–67 ng/mL), fentanyl, heroin, acetaminophen and caffeine, within 13 min. In most cases, the regioisomeric fluorofentanyls were resolved from each other except for the 3′- and 4′-fluorinated derivatives (5b and 5c). To achieve full separation, an orthogonal benchtop 19F NMR method allows the identification and quantification of target analogues (LOD = 74–400 μg/mL, LOQ = 290–1340 μg/mL). The 19F NMR method allows the detection of fluorinated fentanyl analogues at a low concentration (2.4%w/w) in heroin.