Identification of closely related new psychoactive substances (NPS) using solid deposition gas-chromatography infra-red detection (GC-IRD) spectroscopy.

The challenges associated with the identification of new NPS have become more apparent with the increasing number of new drugs in the market and the need to identify the specific isomer due to legislation concomitant with the lack of reference standards for comparison. A recent new tandem technique, solid deposition gas chromatography-infra red detection spectroscopy (GC-IRD), which incorporates the GC for the separation of the different components in the sample matrix and infrared red (IR) spectroscopy which provides unique IR spectra of each component, has provided the necessary discrimination for the identification of isomers. This paper presents the identification and the application of an algorithm-based criteria (ABC) for the evaluation of the quality match factor (QMF) as an objective critical criteria in determining the correctness of an identification of close analogues in four classes of compounds; namely the JWH-018 and its structural isomers, AM-2201 and its fluoro positional isomers in the pentyl group, methylmethcathinone (MMC) and its methyl positional isomers in the phenyl ring, and dibutylone and its close analogues.

Tamoxifen-like metallocifens target the thioredoxin system determining mitochondrial impairment leading to apoptosis in Jurkat cells.

Tamoxifen-like metallocifens (TLMs) of the group-8 metals (Fe, Ru, and Os) show strong anti-proliferative activity on cancer cell lines resistant to apoptosis, owing to their unique redox properties. In contrast, the thioredoxin system, which is involved in cellular redox balance, is often overexpressed in cancer cells, especially in tumour types resistant to standard chemotherapies. Therefore, we investigated the effect of these three TLMs on the thioredoxin system and evaluated the input of the metallocene unit in comparison with structurally related organic tamoxifens. In vitro, all three TLMs became strong inhibitors of the cytosolic (TrxR1) and mitochondrial (TrxR2) isoforms of thioredoxin reductase after enzymatic oxidation with HRP/H2O2 while none of the organic analogues was effective. In Jurkat cells, TLMs inhibited mainly TrxR2, resulting in the accumulation of oxidized thioredoxin 2 and cell redox imbalance. Overproduction of ROS resulted in a strong decrease in the mitochondrial membrane potential, translocation of cytochrome c to the cytosol and activation of caspase 3, thus leading to apoptosis. None of these events occurred with organic tamoxifens. The mitochondrial fraction of cells exposed to TLMs contained a high amount of the corresponding metal, as quantified by ICP-OES. The lipophilic and cationic character associated with the singular redox properties of the TLMs could explain why they alter the mitochondrial function. These results provide new insights into the mechanism of action of tamoxifen-like metallocifens, underlying their prodrug behaviour and the pivotal role played by the metallocenic entity in their cytotoxic activity associated with the induction of apoptosis.