Synthetic cannabinoids in e-liquids: A proton and fluorine NMR analysis from a conventional spectrometer to a compact one.

Highlights

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NMR was applied to the analysis of e-liquids containing synthetic cannabinoids.

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The 1H NMR profiles of 13 samples of e-liquids were obtained with HF and LF NMR.

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Fluorinated synthetic cannabinoids were quantified using HF and LF 19F NMR.

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Quantitative results were obtained for the five synthetic cannabinoids detected.

The 1H NMR profiles of 13 samples of e-liquids supplied by French customs were obtained with high-field and low-field NMR. The high-field 1H NMR spectra allowed the detection of matrix signals, synthetic cannabinoids, and flavouring compounds. Quantitative results were obtained for the five synthetic cannabinoids detected: JWH-210, 5F-MDMB-PICA, 5F-ADB, 5F-AKB48, and ADB-FUBINACA. Conventional GC-MS analysis was used to confirm compound identification. Fluorine-19 NMR was proposed for the quantification of fluorinated synthetic cannabinoids and was successfully implemented on both 400 MHz and 60 MHz NMR spectrometers. This study based on few examples explored the potentiality of low-field NMR for quantitative and quantitative analysis of synthetic cannabinoids in e-liquids.

Electronic cigarettes or e-cigarettes have spread rapidly in recent years as an alternative method for nicotine delivery. Compared to traditional tobacco, they are inexpensive, easy to use, and described as safer for public health [1], [2] although they have been associated with a variety of health effects, particularly the exposure to some constituents of aerosols that might result in respiratory complications [3], [4]. Electronic liquids or e-liquids are formulations used in e-cigarettes which can vaporize aerosol for inhalation when the e-cigarette is activated. E-liquids usually contain a mixture of propylene glycol (PG) and glycerol as the main matrix but also flavours and in some case a pharmaceutical and/or herbal agent inside [5], [6].

Synthetic cannabinoids (SCs) are the most rapidly growing class of recreational designer drugs used in e-liquids [6], [7], [8]. Their chemical structures differ from naturally occurring cannabinoids, but they have similar pharmacological activities by binding with CB1 and/or CB2 receptors [9]. SCs could enhance the excitatory effect by promoting the ability to pass the blood-brain barrier because of chemical structure modifications reducing the molecular polarity [10]. SCs were originally used as therapeutic drugs for their anti-convulsant, anti-nociceptive, and anti-psychotic properties, but long time inhalation or high dose intake can induce addiction, cardiovascular disease, mental confusion, high blood pressure, seizures, acute kidney injury, cancer, and even death [11]. SCs usually exhibit more potency than natural cannabis as they are designed to bind more strongly to CB1/CB2 receptors in the neuronal system [12], and they also may interact with other receptors in the brain that natural cannabis does not [13]. Due to the fast generation of SCs, their structures are quite diverse and a large number of new psychoactive SCs have appeared on sale, which makes it even more difficult to detect and distinguish them [14]. Over the past decade, various studies have described the detection of SCs, most of them focusing on the identification and structural characterization of new cannabinoids [15], [16], [17], [18], [19], [20], [21]. In addition to these researches, the use of different analytical methods for the detection or/and quantification of SCs in commercial herbal mixture blends has become a vibrant area of research [22], [23], [24], [25], [26], [27], [28], [29]. However, only a few studies on screening for SCs or natural cannabinoids in e-liquids have been reported. Peace and co-workers have identified SCs and other components in commercially available e-liquid formulations using direct analysis in real time mass spectrometry (DART-MS) and gas chromatography-mass spectrometry (GC-MS), as well as naturally occurring cannabinoids quantified by high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS/MS) [5], [7], [30]. Poklis et al. evaluated 5F-ADB in 9 cannabidiol e-liquids from the same manufacturer by DART-MS and GC-MS in 2019 [8].

Nuclear Magnetic Resonance (NMR) spectroscopy has already been described as a powerful method for the analysis of complex mixtures and recent review articles summarized the promising capabilities of NMR in the fields of forensic and fraud analysis for both qualitative and quantitative purposes [31], [32], [33]. Concerning SCs, NMR was used for their structural identification and for the analysis of herbal blends [18], [22], [25], [26], [27], [34]. Although high-field (HF) NMR is not yet considered as a routine tool in analytical chemistry mainly because of its high cost, benchtop cryogen-free low-field (LF) NMR which uses much cheaper instruments can partially solve this cost issue and be implemented in forensic or customs laboratories. Indeed, compact NMR spectroscopy has been applied recently for the quality control of various matrices, including meat [35], edible oils [36], drugs [37], dietary supplements [38], [39] and herbal blends containing cannabinoids [24].

The aim of the present study was to assess the capacity of HF and LF NMR for the characterization of e-liquid contents. Proton (1H) and fluorine (19F) NMR analyses were carried out with both HF (400 MHz for 1H) and LF (60 MHz for 1H) spectrometers and GC-MS was used as a confirmation and reference method. To our knowledge, this study is the first to use compact LF NMR for the characterization of SCs and flavouring agents in e-liquids.