Polarising Poison – Synthesis, characterization and development of rapid, sensitive methods for the detection of potent synthetic opiates

Gilbert, N. (2020) Polarising Poison – Synthesis, characterization and development of rapid, sensitive methods for the detection of potent synthetic opiates. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

The occurrence of synthetic opioid fentanyl and its derivatives has grown significantly in forensic casework in recent years. This poses a threat for public health, as it has been reported that minute quantities of fentanyl are enough to induce an overdose. Approximately 32,400 people died because of synthetic opioids in the United States in 2018, and the current situation has been described as an “opioid epidemic”. The increase in fentanyl abuse has been associated with the emergence of a large variety of fentanyl analogues. These novel compounds are more difficult to identify by forensic chemists and may not be detected when they emerge, because they have yet to be characterised and added to mass spectral databases. Another insidious phenomenon has been contributing to the increase in overdoses: fentanyl and its analogues have often been mixed into or sold as other illicit drugs. Most commonly, fentanyl has been found in heroin samples, a practice which may occur unbeknown to drug users and increase the risk of overdose. This thesis aimed to solve these challenges associated with fentanyl detection, to aid in forensic casework and harm reduction. In Chapter II, eighteen common fentanyl analogues were synthesised, fully characterised, and submitted to presumptive colour tests, TLC and FT-IR analysis. A GC-MS method was developed to separate target analogues and allow their detection and quantification in seized heroin samples. Chapter III focused on fluorofentanyl regioisomers, which could not be separated by GC-MS. An orthogonal benchtop 19F NMR method was developed to differentiate and quantify these analogues. Chapter IV focused on the eosin Y colour test, which can be used to detect fentanyl analogues. The mechanism of the reaction between eosin Y and heroin/fentanyl was investigated by NMR. UV-Vis spectrophotometry and RGB detection were used to develop a quantitative version of the test. Finally, in Chapter V, a principal component analysis (PCA) model based on MS data from fentanyl analogues was developed. The model was able to group analogues based on their structural class and identify structural modifications in novel compounds.