Identification and characterization of α-PVT, α-PBT, and their bromothienyl analogs found in illicit drug products

Abstract

Recently, thienyl derivatives of cathinones have appeared on the market as new psychoactive substances (NPS). In this study, identification and characterization of 2-(pyrrolidin-1-yl)-1-(thiophen-2-yl)pentan-1-one (a-PVT), 2-(pyrrolidin-1-yl)-1-(thiophen-2-yl)butan-1-one (a-PBT), and their bromothienyl analogs disclosed in illicit products are described. In our analysis, some analogous compounds of a-PVT, which had a bromine substitution on the thiophene ring, were identified in the samples containing a-PVT; 1-(4-bromothiophen-2-yl)-2-(pyrrolidin-1-yl)pentan-1-one, 1-(5-bromothiophen-2-yl)-2-(pyrrolidin-1-yl)pentan-1-one, and 1-(4,5-dibromothiophen-2-yl)-2-(pyrrolidin-1-yl)pentan-1-one by comparing the analytical data with synthetic reference standards. We also observed 1-(4-bromothiophen-2-yl)-2-(pyrrolidin-1-yl)butan-1-one and 1-(5-bromothiophen-2-yl)-2-(pyrrolidin-1-yl)butan-1-one from a powder product, in which a-PBT was detected. The brominated a-PVTs were also found when overbrominated 1-(thiophen-2-yl)pentan-1-one reacted with pyrrolidine, and they are suspected to be the by-products of a-PVT synthesis. In Japan, cathinone derivatives with a phenyl group as the aromatic ring have been widely controlled by generic scheduling. To escape from such a regulation, analogs with different aromatic groups such as a-PVT and a-PBT appeared on the illicit market of psychoactive compounds. To our knowledge, this is the first report describing identification of a-PBT, and bromothienyl analogs of both a-PVT and a-PBT in illicit drug products. The synthetic method and analytical data shown in this study will be useful for identification of the thienyl derivatives of cathinone analogs.

Intended and unintended use of cathinone mixtures

“…In 2009, the Dutch Drug Information and Monitoring System reported that variable amounts (96-150 mg/ tablet) of mephedrone were covertly included in tablets sold as MDMA (Dargan, Sedefov, Gallegos, & Wood, 2011). Recently, the analysis of illicit samples revealed that they contained alpha-pyrrolidinobutiothiophenone and α-PVP and their bromothienyl analogues (Doi et al, 2016).…”

Identification and characterization of a putative new psychoactive substance, 2‐(2‐(4‐chlorophenyl)acetamido)‐3‐methylbutanamide, in Spain

“…[5,[11][12][13][14] Consequently, analytical methods to identify and quantify this compound have been developed in forensic toxicology. [18,19] In a previous paper, we described two new methods for the LC-MS/MS detection of propofol in urine and blood through the electrophilic aromatic substitution (EAS) with aryl-diazonium salt (ArN 2 + [15] New methods have been developed in liquid chromatography-tandem mass spectrometry (LC-MS/MS), in particular for the phase II metabolites, as markers of propofol administration.…”

“…Moreover, some of these compounds are non-volatile and thermolabile, requiring additional derivatization steps in GC-MS analysis. [18] X-ray crystallography, especially single-crystal X-ray diffraction, allows an unequivocal characterization of the structure of a molecule, but only if the compound can be formed as X-ray-suitable crystals. [4,[10][11][12] Moreover, HRMS allows screening analyses without reference standards being available (tentative identification).…”

“…[10] Nuclear magnetic resonance (NMR) spectroscopy has proved to be one of the most powerful techniques for the structural elucidation and characterization of organic molecules, and has been applied to the identification and characterization of synthetic cannabinoids [17] and synthetic cathinones. [18] X-ray crystallography, especially single-crystal X-ray diffraction, allows an unequivocal characterization of the structure of a molecule, but only if the compound can be formed as X-ray-suitable crystals. Thus, the combination of spectroscopic and mass spectrometric techniques provides a versatile workflow for structural elucidation, characterization and identification of unknown substances.…”

“…The derivatization methods described in literature for propofol were only focused on the hydroxyl group (ÀOH) reacting with dansyl and N-methylpyridinium groups. [18,19] In a previous paper, we described two new methods for the LC-MS/MS detection of propofol in urine and blood through the electrophilic aromatic substitution (EAS) with aryl-diazonium salt…”