Synthesis, characterization and differentiation of the structural isomers of valine and tert-leucine derived synthetic cannabinoids.

The identification of the synthetic cannabinoids receptor agonists (SCRAs) has always posed a great challenge to drug testing laboratories with slight structural modifications aimed at evading drug legislation. In addition, the most prevalent synthetic cannabinoids have valine and tert-leucine amino acid moieties where re-arrangement of the carbon chains can result in structural isomers that are very similar to the parent synthetic cannabinoids. This makes their analysis and identification challenging, and the problem is compounded with the difficulty in purchasing reference standards quickly and a lack of literature for comparison. Therefore, in this investigation, four series of synthetic cannabinoids (AB-PINACA, AB-CHMINACA, MMB-FUBINACA and 5-fluoro-MDMB-PINACA) and their alkyl chain structural isomers at the amino acid moieties were synthesized and characterized using various analytical techniques-gas chromatography-mass spectrometry (GC-MS), gas chromatography-infrared detection (GC-IRD) and nuclear magnetic resonance (NMR) spectroscopy to evaluate the ability of each analytical technique to differentiate the respective isomers for their identification. A total of 12 isomers were synthesized and analysed together with the four parent synthetic cannabinoids. NMR was able to differentiate between all the compounds, whereas GC-IRD was able to discern between most of the synthetic cannabinoids and their isomers. GC-MS had the least discriminating power and was not able to differentiate some of the compounds that has very similar mass spectra. The results from this work will be useful to other drug testing laboratories that are facing the identification of related synthetic cannabinoids.

Technical note: Unequivocal identification of 5-methoxy-DiPT with NOESY NMR and GC-IRD.

The need for new analytical methods to differentiate isomers and closely related compounds have become increasingly important due to the fast evolution of new psychoactive substances. 2D NMR and GC-IR spectroscopies are promising techniques due to their capabilities to differentiate isomers. This case study highlights specifically the use of Nuclear Overhauser Effect Spectroscopy (NOESY) and solid deposition GC-IRD in the unequivocal identification of 5-methoxy-DiPT, a tryptamine analogue.

Simultaneous analysis of 2Cs, 25-NBOHs, 25-NBOMes and LSD in seized exhibits using liquid chromatography-tandem mass spectrometry: A targeted approach.

Blotter papers laced with lysergic acid diethylamide (LSD) have been abused traditionally for their hallucinogenic properties. In recent years, new psychedelic phenethylamines such as 2,5-dimethoxyphenethylamines (2C) and their N-benzylhydroxy (25-NBOH) and N-2-methoxybenzyl derivatives (25-NBOMe) have emerged in the illicit drugs market. Traditionally, gas chromatography-mass spectrometry (GC-MS) is regarded as the gold standard for illicit drugs analysis. However, with the emergence of new psychoactive substances (NPS) which are thermally labile (such as the 25-NBOH drugs which undergo thermal degradation to their respective 2C drugs), alternative non-thermal techniques have to be developed in order to prevent misidentification. In this study, a single, targeted, non-thermal analytical method using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to simultaneously identify these new phenethylamines and their derivatives was developed and validated. Twelve phenethylamines and their derivatives, as well as LSD were simultaneously analysed using the LC-MS/MS in a multiple reaction monitoring (MRM) detection mode. The method developed was validated and applied for the analysis of phenethylamines and their derivatives commonly found in seized exhibits such as blotter papers and Ecstasy tablets.

Challenges in GC-MS analysis: Case studies on phenibut and ethylphenidate.

The challenges associated with drug analysis using GC-MS such as thermal degradation, cyclisation or unwanted side reactions causing potential erroneous identification have become evident in view of the high surge in new drugs available in the market. Two case studies illustrated how alternative methods or modifications to existing techniques can help to circumvent the limitations. In the first case study, phenibut which is a GABA analogue, cyclises to 4-phenyl-2-pyrrolidinone under thermal conditions. The identification of phenibut was achieved through derivatisation and identification of its TMS derivative. The second case study, thermal degradation was minimised on drugs of interest methylphenidate and ethylphenidate by reducing the injector port temperature to 200°C and maintaining the GC oven temperature at below 190°C in order to prevent thermal degradation of the drugs of interest.