Synthetic opioids, such as fentanyl and its analogues, are a new public health warning. Clandestine laboratories produce drug analogues at a faster rate than these compounds can be controlled or scheduled by drug agencies. Detection requires specific testing and clinicians may be confronted with a sequence of severe issues concerning the diagnosis and management of these contemporary opioid overdoses. This paper deals with methods for biological sample treatment, as well as the methodologies of analysis that have been reported, in the last decade, in the field of fentanyl-like compounds. From this analysis, it emerges that the gold standard for the identification and quantification of 4-anilinopiperidines is LC-MS/MS, coupled with liquid-liquid or solid-phase extraction. In the end, the return to the scene of illicit fentanyls can be considered as a critical problem that can be tackled only with a global multidisciplinary approach.
Keywords: Fentanyl; designer opioids; fentanyl-like compounds; illicit fentanyls; mass spectrometry.