Folker Westphal

Mass and NMR spectroscopic characterization of 3,4-methylenedioxypyrovalerone: A designer drug with α-pyrrolidinophenone structure

This study presents and discusses the nuclear magnetic resonance (NMR) spectroscopic and mass spectroscopic data of the designer drug 3,4-methylenedioxypyrovalerone (MDPV), a drug variant of pyrovalerone. MDPV was first seized in Germany in the year 2007. The structure elucidation of the aliphatic part of MDPV was carried out by product ion spectroscopy of the immonium ion with m/z 126 formed after electron ionization, and by 1D (1)H and (13)C NMR spectroscopy. Additional two-dimensional NMR spectroscopy was used to verify the structure of the alkyl side chain, and to determine the methylenedioxy position in the aromatic ring.

Mass, NMR and IR spectroscopic characterization of pentedrone and pentylone and identification of their isocathinone by-products

This study presents and discusses the mass spectrometric, nuclear magnetic resonance spectroscopic and infrared spectroscopic data of the designer drugs pentedrone (2-methylamino-1-phenylpentan-1-one) and its methylenedioxy analog pentylone (2-methylamino-1-(3,4-methylenedioxyphenyl)pentan-1-one). The structure elucidation of the aliphatic parts was carried out by product ion spectroscopy of the immonium ion with m/z=86 formed after electron ionization, and by one- and two-dimensional (1)H- and (13)C-NMR spectroscopy on the hydrochloride salts to verify the structure of the alkyl side chain and to determine the methylenedioxy position in the aromatic ring of pentylone. Furthermore, two typical cathinone synthesis by-products were detected besides the main compounds. Their mass spectra are discussed and for one of them (1-methylamino-1-phenylpentan-2-one (isopentedrone)) a NMR assignment was possible in the existing mixture.

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.

Spectroscopic characterization of 3,4-methylenedioxypyrrolidinobutyrophenone: A new designer drug with α-pyrrolidinophenone structure

This study presents and discusses the infrared spectroscopic, the nuclear magnetic resonance spectroscopic and mass spectrometric data of the designer drug 3,4 methylenedioxypyrrolidinobutyrophenone (MDPBP), a homolog of 3,4 methylenedioxypyrovalerone (MDPV). MDPBP was first seized in Germany in the year 2009. The structure elucidation of the aliphatic part of MDPBP was carried out by product ion spectrometry of the immonium ion with m/z=112 formed after electron ionization, and by one- and two-dimensional (1)H- and (13)C NMR spectroscopy.

Ring positional differentiation of isomeric N-alkylated fluorocathinones by gas chromatography/tandem mass spectrometry

In analogy to our previously published procedure for the differentiation of regioisomeric fluoroamphetamines a method was developed, to differentiate ring positional isomeric fluorocathinones by product ion spectrometry of ions generated by chemical ionization (CI) under GC-MS conditions using methane as reagent gas. N-alkylated ortho-, meta- and para-fluorocathinones could be unequivocally differentiated by product ion spectrometry of the hydrogen fluoride loss ions [M+H-HF](+) using a triple quadrupole mass spectrometer with argon as collision gas under normalized collision conditions. This method enables the differentiation of ring positional isomers of fluorocathinones even in complex mixtures and low concentrations. The applicability of the method was shown by the analysis of synthesized N-alkylated ortho-, meta- and para-fluorocathinones and seized designer drug mixtures.

Structure elucidation of a new designer benzylpiperazine: 4-Bromo-2,5-dimethoxybenzylpiperazine

A new designer benzylpiperazine was seized in Germany for the first time. Interpreting the results of gas chromatography-mass spectroscopy (GC-MS), product ion spectroscopy (GC-MS/MS), and nuclear magnetic resonance (NMR) spectroscopy the compound was 4-bromo-2,5-dimethoxybenzylpiperazine. The structure of the new benzylpiperazine was finally proved by two-dimensional NMR correlations and by GC-MS after synthesis of two of the possible isomers from commercially available starting materials. Additionally mass spectroscopic data after liquid chromatography-mass spectroscopy (LC-MS/MS) using electrospray ionization (ESI) as well as ultraviolet (UV) spectral data of the new compound are presented. A small quantity of the new benzylpiperazine was seized in very high purity along with other also very pure designer drugs in Hamburg, Germany.

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.

Analytical characterization of four new ortho-methoxybenzylated amphetamine-type designer drugs.

In a seizure of German custom authorities four N-(ortho-methoxybenzyl)amines with amphetamine partial structure were obtained as pure compounds: N-(ortho-methoxybenzyl)-3,4-dimethoxyamphetamine (3,4-DMA-NBOMe (1)), N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe (2)), N-(ortho-methoxybenzyl)-4-methylmethamphetamine (4-MMA-NBOMe (3)), and N-(ortho-methoxybenzyl)-5-(2-aminopropyl)benzofuran (5-APB-NBOMe (4)). 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. Copyright

LC-high resolution-MS/MS for identification of 69 metabolites of the new psychoactive substance 1-(4-ethylphenyl-)-N-[(2-methoxyphenyl)methyl] propane-2-amine (4-EA-NBOMe) in rat urine and human liver S9 incubates and comparison of its screening power with further MS techniques

Abstract4-EA-NBOMe (N-(2-methoxybenzyl)-4-ethylamphetamine, 1-(4-ethylphenyl-)-N-[(2-methoxyphenyl)methyl]propane-2-amine) is an amphetamine-derived new psychoactive substance (NPS) of the N-methoxybenzyl (NBOMe) group first seized by German custom authorities. In contrast to the phenethylamine NBOMes, studies on the pharmacological, toxicological, or metabolic properties are not yet published. The aims of the presented work were the use of LC-HR-MS/MS for identification of the phase I and II metabolites of 4-EA-NBOMe in rat urine and pooled human S9 fraction (pS9) incubations, to compare metabolite formation in both models, to identify involved monooxygenases, and to elucidate its detectability in standard urine screening approaches (SUSAs) using GC-MS, LC-MSn, and LC-HR-MS/MS. 4-EA-NBOMe was mainly metabolized by oxidation of the ethyl group to phenyl acetaldehyde, to benzoic acid, or to phenylacetic acid, by hydroxylation, and all combined with O-demethylation as well as by glucuronidation and sulfation of the main phase I metabolites in rats. With the exception of the oxidation to benzoic acid, all main metabolic reactions could be confirmed in the incubations with pS9. In total, 36 phase I and 33 phase II metabolites could be identified. Monooxygenase activity screenings revealed the general involvement of cytochrome-P450 (CYP) 1A2, CYP2B6, and CYP3A4. An intake of 4-EA-NBOMe was detectable only via its metabolites by all SUSAs after low-dose administration. The main targets for both LC-MS screenings should be the phenylacetic acid derivative, the mandelic acid derivative both with and without additional O-demethylation, and, for GC-MS, the hydroxy metabolite after conjugate cleavage.

Structure elucidation of a new open chain isomer of the cannabimimetic cyclopropoylindole A-796,260

A new hitherto unknown ring opened isomer of the tetramethylcyclopropoylindole 1-(2-morpholin-4-ylethyl)-1H-indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone (A-796,260) has been identified in a seizure of the German Customs. It bears an E-alkene moiety in the side chain with a tert.-butyl group, having a 3-penten-5-one skeleton. The isomer is not identical to the known products of thermal ring opening of tetramethylcyclopropoylindoles, which have a 1-pentene-5-one alkyl chain, instead. We postulate its formation via a Wagner-Meerwein-rearrangement under acidic conditions during the attempted synthesis of the desired tetramethylcyclopropoylindole. Whether the compound, found in high purity, has been the result of a synthesis fault or has been synthesized intentionally and if the new isomer has cannabimimetic potential, is still unknown. During structure elucidation with NMR spectroscopy and mass spectrometry, interesting phenomena have been detected concerning the product ion spectrometry of tetramethylcyclopropoylindoles.