In forensic drug analysis, extractive pretreatment is required prior to instrumental analysis to ensure successful detection of the target compounds. However, conventional extraction methods such as hydrophilic polymer‐based solid‐phase extraction and liquid–liquid extraction are unsuitable for an emerging class of new psychoactive substances, namely, synthetic cathinones, because they exhibit a lack of class selectivity and increased risk of target analyte decomposition during extraction. To address these issues, we describe a highly class‐selective sample clean‐up method for the extraction of synthetic cathinones from urine and whole blood samples, exploiting a molecularly imprinted polymer solid‐phase extraction cartridge. In terms of the influence of the synthetic cathinone molecular structure on the extraction recovery, we showed that while longer alkyl side chains slightly reduced the extraction efficiency, substituent variation on the aromatic ring exerted no effect. Molecularly imprinted polymer solid‐phase extraction of 11 synthetic cathinones from urine samples yielded higher recoveries than the two conventional extraction methods, and smaller matrix effect was observed than that with hydrophilic polymer‐based solid‐phase extraction. Molecularly imprinted polymer solid‐phase extraction from whole blood samples gave recoveries comparable to those of urine samples. Therefore, the proposed method is applicable for the extraction and quantitative determination of synthetic cathinones in biological samples.

Mass spectrometric differentiation of structural isomers is important for the analysis of forensic samples. Presently, there is no mass spectrometric method for differentiating halogen positional isomers of cannabimimetic compounds. We describe here a novel and practical method for differentiating one of these compounds, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA (para)), and its fluoro positional (ortho and meta) isomers in the phenyl ring by electron ionization-triple quadrupole mass spectrometry. It was found that the three isomers differed in the relative abundance of the ion at m/z 109 and 253 in the product ion spectra, while the detected product ions were identical. The logarithmic values of the abundance ratio of the ions at m/z 109 to 253 (ln(A /A )) were in the order meta < ortho < para and increased linearly with collision energy. The differences in abundances were attributed to differences in the dissociation reactivity between the indazole moiety and the fluorobenzyl group because of the halogen-positional effect on the phenyl ring. Our methodology, which is based on the abundance of the product ions in mass spectra, should be applicable to determination of the structures of other newly encountered designer drugs. Copyright © 2016 John Wiley & Sons, Ltd.

PurposePositional isomer differentiation is crucial for forensic analysis. The aim of this study was to differentiate AB-FUBINACA positional isomers using liquid chromatography (LC)–electrospray ionization (ESI)-linear ion trap mass spectrometry (LIT-MS) and LC–ESI-triple quadrupole mass spectrometry (QqQ-MS).MethodsAB-FUBINACA, its two fluorine positional isomers on the phenyl ring, and three methyl positional isomers in the carboxamide side chain were analyzed by LC–ESI-LIT-MS and LC–ESI-QqQ-MS.ResultsFour of the positional isomers, excluding AB-FUBINACA and its 3-fluorobenzyl isomer, were chromatographically separated on an ODS column in isocratic mode. ESI-LIT-MS could discriminate only three isomers, i.e., the 2-fluorobenzyl isomer, the N-(1-amino-2-methyl-1-oxobutan-2-yl) isomer, and the N-(1-amino-1-oxobutan-2-yl)-N-methyl isomer, based on their characteristic product ions observed at the MS3 stage in negative mode. ESI-QqQ-MS differentiated all six isomers in terms of the relative abundances of the product ions that contained the isomeric moieties involved in collision-induced dissociation reactions. The six isomers were more clearly and significantly differentiated upon comparison of the logarithmic values of the product ion abundance ratios as a function of collision energy.ConclusionsThe present LC–MS methodologies were useful for the differentiation of a series of AB-FUBINACA positional isomers.Electronic supplementary materialThe online version of this article (10.1007/s11419-018-0410-4) contains supplementary material, which is available to authorized users.

A reliable method for structural analysis is crucial for the forensic investigation of new psychoactive substances (NPSs). Towards this end, mass spectrometry is one of the most efficient and facile methods for the identification of NPSs. However, the differentiation among 2-, 3-, and 4-fluoromethcathinones (o-, m-, and p-FMCs), which are ring-fluorinated positional isomers part of the major class of NPSs referred to as synthetic cathinones, remains a challenge. This is mostly due to their similar retention properties and nearly identical full scan mass spectra, which hinder their identification.

We present herein a practical methodology for elucidating the o-, m-, or p‰uorine substitution pattern of indazole-type synthetic cannabinoids containing a ‰uorobenzyl group at the N-1 position and a carbonyl group at the C-3 position via electron ionization-triple quadrupole mass spectrometry. We synthesized, as model compounds of the synthetic cannabinoids, the o-, m-, and p-‰uorine positional isomers: 1-[1-(2-, 3-, and 4-‰uorobenzyl)-1H-indazol-3-yl]ethanone (o-, m-, and p-FUBINAE). Mass spectral analyses showed that the three isomers diŠered signiˆcantly in the logarithmic values of the abundance ratios of the product ion at m/z 109 to the precursor ion at m/z 253 (ln(A 109 /A 253 )), following the order of meta＜ortho＜para. In addition, the relationships between ln(A 109 /A 253 ) and collision energy were linear with high correlation coe‹cients. Comparing the ln(A 109 /A 253 ) plots of the FUBINAE isomers versus collision energy with similar plots of AB-FUBINACA and its o-and m-‰uorobenzyl isomers showed that the three AB-FUBINACA isomers behaved as the FUBINAE isomers did with the same ‰uorine substitution pattern on the phenyl ring. Moreover, other synthetic cannabinoids with a p-‰uorobenzyl group (ADB-FUBINACA, FUB-AMB, FUB-APINACA, FUB-NPB-22, and FU-PX-2) also exhibited behavior similar to p-FUBINAE. These results indicated that the ‰uorine substitution position on the phenyl ring can be diŠerentiated by collating the model compounds according to the logarithmic plots of their mass spectral abundance ratios as a function of the collision energy.