Laura M. Huppertz

Characterization of the four designer benzodiazepines clonazolam, deschloroetizolam, flubromazolam, and meclonazepam, and identification of their in vitro metabolites

In 2012, the first designer benzodiazepines were offered in Internet shops as an alternative to prescription-only benzodiazepines. Soon after these compounds were scheduled in different countries, new substances such as clonazolam, deschloroetizolam, flubromazolam, and meclonazepam started to emerge. This article presents the characterization of these four designer benzodiazepines using nuclear magnetic resonance spectroscopy, gas chromatography–electron ionization-mass spectrometry, liquid chromatography–tandem mass spectrometry, liquid chromatography–quadrupole time-of-flight-mass spectrometry, and infrared spectroscopy. The major in vitro phase I metabolites of the substances were investigated using human liver microsomes. At least one monohydroxylated metabolite was identified for each compound. Dihydroxylated metabolites were found for deschloroetizolam and flubromazolam. For clonazolam and meclonazepam, signals at mass-to-charge ratios corresponding to the reduction of the nitro group to an amine were observed. Desalkylations, dehalogenations, or carboxylations were not observed for any of the compounds investigated. Furthermore, for clonazolam and meclonazepam, no metabolites formed by a combination of reduction and mono-/dihydroxylation were detected. This knowledge will help to analyze these drugs in biological samples.

Two thiazolylindoles and a benzimidazole: Novel compounds on the designer drug market with potential cannabinoid receptor activity

In a seizure of German customauthorities two 3-([1,3]-thiazol-2-yl)indoles (N-(2-methoxyethyl),N-iso-propyl-2-(1-pentyl-1H-indol-3-yl)-4-thiazolemethanamine (1) and N,N-diethyl-2-(1-pentyl-1H-indol-3-yl)-4-thiazolemethanamine (2)) and one benzimidazole (1-(cyclohexylmethyl)-2-[(4-ethoxyphenyl)methyl]-N,N-diethyl-1H-benzimidazole-5-carboxamide (6)) were seized as pure compounds. The compounds have been detected in Germany for the first time, and no analytical data had been previously published. Mass spectrometric (MS), infrared (IR) spectroscopic, and nuclear magnetic resonance (NMR) spectroscopic data are presented and the way of the structure elucidation of these rather uncommon compounds is discussed.

Betel Nut Chewing in Iron Age Vietnam? Detection of Areca catechu Alkaloids in Dental Enamel

ABSTRACT The betel quid is one of the most commonly consumed psychoactive substances in the world. By archaeological evidence like the occurrence of areca nuts in archaeological sites, the typical overall reddish-brown staining on prehistoric human teeth or specific artifacts linked with the habit, it is assumed that this tradition reaches back to prehistoric times. Since this kind of evidence is indirect, it is frequently doubted. The present study provides the earliest direct analytical indication of betel nut chewing in human history. A typical stained tooth from an Iron Age skeleton (site Gò Ô Chùa in Southern Vietnam, 400–100 BC) was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-high-resolution mass spectrometry (LC-HR-ToF-MS) and the alkaloid arecoline which is specific for Areca catechu L. (Arecaceae) was detected.

Phase I metabolism of the recently emerged synthetic cannabinoid CUMYL-PEGACLONE and detection in human urine samples

Indole-, indazole-, or azaindole-based synthetic cannabinoids (SCs), bearing a cumyl substituent are a widespread, recreationally used subgroup of new psychoactive substances (NPS). The latest cumyl-derivative, CUMYL-PEGACLONE, emerged in December 2016 on the German drug market. The substance features a novel γ-carboline core structure, which is most likely synthesized to bypass generic legislative approaches to control SCs by prohibiting distinct core structures. Using liquid chromatography-tandem mass spectrometry and liquid chromatography-high resolution mass spectrometry techniques, the main in vivo phase I metabolites of this new substance were detected. A pooled human liver microsome assay was applied to generate in vitro reference spectra of CUMYL-PEGACLONE phase I metabolites. Additionally, 30 urine samples were investigated leading to 22 in vivo metabolites. A metabolite mono-hydroxylated at the γ-carbolinone core system and a metabolite with an additional carbonyl group at the pentyl side chain were evaluated as highly specific and sensitive markers to proof CUMYL-PEGACLONE uptake. Moreover, 3 immunochemical assays commonly used for SC screening in urine were tested for their capability of detecting the new drug but failed due to insufficient cross-reactivity.