Hao Wu

Rationale: Phenylethylamines are one of the most common types of new psychoactive substances, following synthetic cannabinoids and synthetic cathinones. They are regulated in many countries because of their strong hallucinogenic effects, which can cause serious nerve damage. There is a wide variety of phenylethylamines, exhibiting rapid renewal and extremely similar structures, therefore accurate qualitative analysis of isomers is a difficult problem in current drug analysis. Methods: The dissociation pathways of the position isomers 2‐(2‐methylaminoprolyl)benzofuran (2‐MAPB) and 5‐(2‐methylaminopropyl)benzofuran (5‐MAPB) were investigated by gas chromatography–mass spectrometry and liquid chromatography coupled to high‐resolution quadrupole Orbitrap MS. The dissociation patterns of the phenethylamine‐based designer drugs 2‐MAPB and 5‐MAPB were explored and extended in this work based on MS combined with density functional theory studies. Results: For electron ionization mass spectrometry (EI‐MS) analysis, the dissociation patterns of 2‐MAPB were similar to those of 5‐MAPB. For electrospray ionization mass spectrometry (ESI‐MS ⁿ ) analysis, the hydrogen atom on amino group was facile to form a intramolecular hydrogen bond with the oxygen atom on the parent nucleus of benzofuran in the structure of 2‐MAPB, leading to higher abundance of the product ion at m / z 58. However, there was a conjugated system between the positive charge formed by the cleavage of the 5‐MAPB side chain and the benzofuran ring, enabling the 5‐MAPB to generate a product ion at m / z 131. Computational study showed that energy barrier and spin density difference distribution jointly control the selective dissociation in EI‐MS, while different types of orbital interaction induced by intramolecular hydrogen bond led to different dissociation results in ESI‐MS ⁿ . Conclusions: These different dissociation patterns could be used to distinguish 2‐MAPB from 5‐MAPB. This could assist forensic laboratories in the differentiation and characterization of potential isomers in these kinds of compounds, especially in mixtures.

Ketamine analogues have been emerging in recent years and are causing severe health and social problems worldwide. Ketamine analogues use 2-phenyl-2-aminocyclohexanone as the basic structure and achieve physiological reactions similar to or even more robust than the prototype of ketamine by changing the substituents on the benzene ring (R₁ and R₂) and amine group (R_N1). Therefore, the mass spectrometry (MS) fragmentation pathways and fragments of ketamine analogues have certain regularity. Eight ketamine analogues are systematically investigated by GC-QTOF/MS and LC-Q-Orbitrap MS/MS with the positive mode of electrospray ionization. The MS fragmentation patterns of ketamine analogues are summarized according to high-resolution MS data. The α-cleavage of carbon bond C₁-C₂ in the cyclohexanone moiety and further losses of CO, methyl radical, ethyl radical and propyl radical are the characteristic fragmentation pathways of ketamine analogues in EI-MS mode. The loss of H₂O or the sequential loss of R_N1NH₂, CO and C₄H₆ are the distinctive fragmentation pathways of ketamine analogues in ESI-MS/MS mode. Moreover, these MS fragmentation patterns are first introduced for the rapid screening of ketamine analogues in suspicious powder. Furthermore, the structure of the ketamine analogue in suspicious powder is 2-(Methylamino)-2-(o-tolyl)cyclohexan-1-one, which is further confirmed by NMR. This study contributes to the identification of the chemical structure of ketamine analogues, which can be used for the rapid screening of ketamine analogues in seized chemicals.

Rationale: Synthetic cannabinoids are some of the most used and abused new psychoactive substances, because they can produce a stronger intense pleasure than natural cannabis. Most of the new synthetic cannabinoids are structurally similar to existing synthetic cannabinoids and can be obtained by modifying partial structures of the latter without changing their effects. Therefore, the derivatization rules and common fragmentation patterns of synthetic cannabinoids could be used for rapid screening and structural identification of them. Methods: The derivatization rules of synthetic cannabinoids are summarized, and the common fragmentation pattern of synthetic cannabinoids including three typical cleavage pathways was explored and extended in this work based on combined mass spectrometry (MS) and density functional theory studies. Five synthetic cannabinoids in electronic cigarette oil from a drug case were separated and characterized using gas chromatography with MS and liquid chromatography coupled to high‐resolution quadrupole Orbitrap MS. Results: The structures of five synthetic cannabinoids in seized electronic cigarette oil were deduced from electron impact ion source (EI) MS and high‐resolution electrospray ionization (ESI) MS ⁿ data, along with the derivatization rules and common fragmentation pattern of synthetic cannabinoids. The proposed structures of these synthetic cannabinoids were further verified via reference substances. Computational study showed that selective cleavage of these compounds was mainly controlled by spin population in EI‐MS, but a tunneling effect arose from proton transfer in ESI‐MS ⁿ detection, which has been rarely reported in previous works. Conclusions: Our results showed that EI‐MS was suitable for identifying synthetic cannabinoids with aromatic ketone structure, which could also be extended to adamantane linked group. Nevertheless, synthetic cannabinoids with carbamoyl linked group were better characterized by high‐resolution ESI‐MS ⁿ compared to EI‐MS. This study demonstrated a method with promising potential for rapid and reliable screening of synthetic cannabinoids in mixtures with enhanced detection throughput and operation simplicity.