Forensic electrochemistry applied to the sensing of new psychoactive substances: electroanalytical sensing of synthetic cathinones and analytical validation in the quantification of seized street samples.

The electrochemical sensing of new psychoactive substance(s) (NPSs), synthetic cathinone derivatives also termed "legal highs", are explored with the use of metallic modified screen-printed electrochemical sensors (SPES). It is found that no significant electrochemical enhancement is evident with the use of either in situ bismuth or mercury film modified SPES compared to the bare underlying electrode substrate. In fact, the direct electrochemical reduction of the cathinone derivatives mephedrone (4-methylmethcathinone; 4-MMC) and 4'-methyl-N-ethylcathinone (4-methylethcathinone; 4-MEC) is found to be possible for the first time, without heavy metal catalysis, giving rise to useful voltammetric electroanalytical signatures in model aqueous buffer solutions. This novel electroanalytical methodology is validated toward the determination of cathinone derivatives (4-MMC and 4-MEC) in three seized street samples that are independently analyzed with high-performance liquid chromatography (HPLC) wherein excellent agreement between the two analytical protocols is found. Such an approach provides a validated laboratory tool for the quantification of synthetic cathinone derivatives and holds potential for the basis of a portable analytical sensor for the determination of synthetic cathinone derivatives in seized street samples.

Elucidation of the Phase I and Phase II metabolic pathways of (±)-4'-methylmethcathinone (4-MMC) and (±)-4'-(trifluoromethyl)methcathinone (4-TFMMC) in rat liver hepatocytes using LC-MS and LC-MS².

(±)-4'-Methylmethcathinone hydrochloride [(±)-mephedrone, 4-MMC] is a synthetic "legal high", with a classical cathinone structure similar to methcathinone. In this study, the in vitro metabolism of 4-MMC was investigated in Sprague-Dawley rat hepatocytes to characterise the associated Phase I and II metabolites. 4-MMC was incubated with rat liver hepatocytes, and the reaction mixture was analysed on a zwitterionic hydrophilic interaction (ZIC-HILIC) column using LC-MS and LC-MS(2). 4-MMC was metabolised, yielding 17 metabolites. These metabolites were structurally characterised on the basis of accurate mass analyses and LC-MS(2) fragmentation patterns and the major metabolic routes for 4-MMC determined to be via (i) oxidation of the 4'-methyl group and (ii) reduction of the ß-keto moiety. The biotransformation of a modified 4'-trifluoromethyl- derivative (4-TFMMC) has also been studied and shows significant differences in its metabolism compared to 4-MMC. Key pharmacokinetic parameters for both drugs have been calculated [biological half-lives (t(½)) for 4-MMC=61.9 min and for 4-TFMMC=203.8 min] and this data may aid in the understanding of in vivo metabolism and the likely pharmacokinetic effects of chemical/structural modifications within this class of controlled substances.

Synthesis, full chemical characterisation and development of validated methods for the quantification of the components found in the evolved "legal high" NRG-2.

The recent global increase in the abuse of 4'-methylmethcathinone (mephedrone) and related compounds has developed a requirement for full chemical characterisation of these products. This work presents full synthetic and chemical characterisation data for the hydrobromide salts of two mephedrone derivatives: 4'-methyl-N-ethylcathinone (4-MEC) and 4'-methyl-N-benzylcathinone (4-MBC) which have been identified in samples of the "legal high" NRG-2. The first fully validated chromatographic methods for the detection and quantitative analysis of these substances both in their pure form and in the presence of a number of common adulterants used in illicit drug manufacture is also reported.