Ultraviolet-Visible and High-Resolution Mass Spectrometry for the Identification of Cyclopropyl-Fentanyl in the First Fatal Case in Spain

Abstract

Here we report the identification and quantitation of cyclopropyl-fentanyl in a fatality casework occurred due to a poly-drug toxicity in Spain in December 2017. The cyclopropyl-fentanyl was identified in non-biological (paraphernalia) and biological samples (whole-blood, vitreous humor and urine). Conventional techniques (GC-MS) and the UV-Vis spectral allowed differencing between the two structural isomer compounds of fentanyl (cyclopropyl and crotonyl) when the CRM was not available at the laboratory. Both of the drugs have the same MS spectra but different UV-Vis spectra due to the presence of an additional chromophore group in the case of crotonyl. The cyclopropyl-fentanyl detection allowed generating an alert and contributing to the surveillance and detection of this dangerous substance found mixed in doses of clandestine sale heroin. Then, high-resolution analytical techniques (LC-HRMS-MS), showed limitations for the identification of the isobaric fentanyl compounds but they had a high potential for fentanyl metabolites identification. Two tentative metabolites were identified in urine samples: cyclopropyl-norfentanyl and N-methyl cyclopropyl-norfentanyl. Finally, the systematic routine method (LC-MS-MS) was validated and applied to the quantification of cyclopropyl-fentanyl in a blood sample. A obtained value (20.4 ng/mL) was in the range of those reported in other cases in different countries (from 8 to 30 mg/ mL), being the determined concentration of cyclopropyl-fentanyl high enough to infer that this fentanyl analog had a main role as cause of death. As far as we know, this is the first fatality reported in Spain involving cyclopropyl-fentanyl.