Hitting the Jackpot – development of gas chromatography–mass spectrometry (GC–MS) and other rapid screening methods for the analysis of 18 fentanyl‐derived synthetic opioids

Abstract

In recent years, the occurrence of synthetic opioid fentanyl and its derivatives has grown significantly in forensic casework. This study presents the synthesis and analysis of 18 fentalogs, selected based on information received from local law enforcement. This study provides colorimetric tests, thin‐layer chromatography (TLC) which can potentially be utilized for presumptive screening of the target compounds, as bulk powders or as trace‐level adulterants. The fully validated confirmatory GC–MS method (employing SIM mode) allows the identification of the 18 derivatives, five commonly encountered controlled substances and four adulterants, within 20 minutes. The cross‐validated method described herein provides a sensitive screening and quantitation method for the illicit (and potentially harmful) components at trace levels (LOD = 0.007–0.822 μg/mL and LOQ = 0.023–2.742 μg/mL respectively). Spectral data [1H‐NMR, 13C‐NMR, 19F‐NMR, FT‐IR, and HRMS] and assignments for the synthesized reference materials are also provided in the Supplementary Information for laboratories engaged in the routine analysis of fentanyl and its derivatives.

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

“…This concentration was based on previously reported studies of seized samples within Greater Manchester. [41] Due to the small sample size (n = 7) in these previous studies, the results may not truly reflect the typical levels of fentanyl contained in heroin samples nationally. However, this concentration was chosen to demonstrate that the proposed low-field qNMR method is suitable for the routine screening of suspect samples which may contain fentanyl derivatives at trace levels.…”

“…The solvent system was selected to directly relate the chromatographic data of these novel fluorinated fentanyl derivatives with previously reported fentalogues. [41] The developed plates were observed under UV light (254 nm) and developed with modified Dragendorff-Ludy-Tenger reagent. [42] Six replicate tests were conducted for each compound to calculate the average retention factor (Rf) and relative retention factor (RRf, with respect to fentanyl, 18).…”

“…This difference in sensitivity must be considered when screening samples in scan mode, as low concentrations of fentalogues may not be detected. [41] The accuracy (percentage recovery study) of the method was determined using a percentage recovery study (see Supplementary Information, Table S5). Spiked samples were prepared in triplicates at three concentration levels over a range of 80-120% of a target concentration (15 μg/mL).…”

Development and evaluation of a synthetic opioid targeted gas chromatography mass spectrometry (GC‐MS) method

“…Since GC-MS is an extensively used technique for fentanyl analysis [30], developing tools and methods using this platform could allow for adoption by a large number of laboratories. Much of the recent work that has been method-based has focused on small subsets of compounds [31] or has been toxicology focused [32,33]. In terms of novel data analysis and interpretation, Gilbert et al demonstrated how principal component analysis can be used for the classification of fentanyl analogues based on their gas chromatography mass spectrometry (GC-MS) spectra [34].…”

Suspect Screening of Fentanyl Analogs Using Matrix-Assisted Ionization and a Miniature Mass Spectrometer with a Custom Expandable Mass Spectral Library

“…In addition, analytical methods need to be regularly updated to keep up with the constant emergence of new uncontrolled analogs. Currently, some methods have been reported for the determination of fentanyl and its derivatives, such as thin-layer chromatography, high-performance liquid chromatography (HPLC) with ultraviolet and amperometric detection, − gas chromatography–mass spectrometry (GC–MS), ,− HPLC − or ultrahigh-performance liquid chromatography (UHPLC) − coupled with triple quadrupole or linear ion trap mass spectrometers, etc. Featuring high specificity and selectivity, GC–MS and (U)­HPLC–MS are gold standard methods for drug analysis.…”