Rapid qualitative and quantitative analysis of novel drug analogues via Desorption Electrospray Ionisation - Mass Spectrometry (DESI-MS)

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Desorption electrospray ionisation - mass spectrometry (DESI-MS) is an ambient ionisation technique that can be applied to the analysis of illicit drugs and novel drug analogues in seized drug material. Currently used preliminary identification techniques lack sensitivity and selectivity and are prone to false positive and false negative results. Therefore, it was important to investigate the use of DESI-MS as a novel preliminary identification technique in the analysis of a range of compounds with the potential for future automated library matching aiding in the rapid identification of unknowns. In this research, 4-methylmethcathinone (mephedrone or 4-MMC), cocaine, 1-benzylpiperazine (BZP), 3-trifuoromethylphenylpiperazine (TFMPP), 3-chlorophenylpiperazine (mCPP), 4-methoxyphenylpiperazine (MeOPP) and other amphetamine-type substances (ATS) such as amphetamine (AP), methylamphetamine (MA), 3,4-methylenedioxymethylamphetamine (MDMA), N,N-dimethylamphetamine (DMA), 4-methoxyamphetamine (PMA), and 4-methoxymethylamphetamine (PMMA) were the drugs of interest since they are increasingly prevalent drugs of abuse globally. The optimisation of the technique and the application of DESI-MS to the analysis of these compounds were demonstrated. A particularly suitable surface, semi-porous polytetra fluoroethylene (PTFE, Teflon) was utilised, as it gave superior signal stability and reproducibility as compared to other surfaces (polymethyl methacrylate (pMMA) and polyvinyl chloride (PVC)). The limits of detection (LOD) of 4-MMC and the piperazine analogues were determined to range between 0.0023 - 2.30 μg/mm². The LOD of the ATS was determined to be in the range 0.02 - 2.80 μg/mm². DESI-MS was also utilised in the preliminary analysis of illicit cocaine samples. The LOD of cocaine was determined to be 3.47 μg/mm². The chemical profiles obtained using DESI-MS were also compared to two current confirmatory analysis techniques, gas chromatography – mass spectrometry (GC-MS) and liquid chromatography – mass spectrometry (LC-MS). The by-products and impurities detected were used to link samples to their synthetic route of manufacture and to the precursors used. The detection of truxillines in the seized cocaine samples aided in determining their geographical origin. Selectivity and matrix effects were evaluated for the compounds of interest in each study. The effect of adulterants including caffeine, procaine, levamisole, lignocaine, paracetamol, and atropine on the detectability of cocaine were investigated. The detectability of ATS were evaluated by adding caffeine, paracetamol, magnesium stearate, and dimethyl sulfone. Piperazine compounds were adulterated using caffeine and a mixture of piperazines (TFMPP and BZP) was also evaluated since these are commonly found in combination. 4-MMC was adulterated with caffeine, paracetamol, MA, phentermine, AP, MDMA, 4-hydroxyamphetamine, 4-fluoroamphetamine, nordiazepam, diazepam, oxazepam, cocaine, heroin, methadone, cathine, cathinone, 4-diethylaminobenzaldehyde, 1-benzyl-3-pyrrolidinol, and methylone. In most cases, despite the presence of ion enhancement or suppression due to the addition of adulterant, the analytes remained detectable. Quantitative experiments for 2 μL spotted solutions of 4-MMC, using codeine-D₆ as an internal standard, introduced in the desorption spray solvent, showed a linear correlation (R² > 0.9840) over the range 50 – 800 μg/mL. The precision for triplicates analysed on five different days (n = 15) was <38 % RSD. The accuracy, expressed as relative error, was <13 %. Identification based on accurate mass and MS/MS spectra aided in discriminating compounds with the same molecular formula. The results obtained using DESI-MS demonstrate its applicability in the rapid qualitative analysis (and preliminary quantitative analysis of 4-MMC) of cocaine, 4-MMC, BZP, TFMPP, mCPP, MeOPP and ATS.
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