Abstract
For more than ten years, new synthetic cathinones (SCs) mimicking the effects of controlled cocaine-like stimulants have flooded the illegal drug market, causing numerous intoxications and fatalities. There are often no data on the pharmacokinetics of these substances when they first emerge onto the market. However, the detection of SC metabolites is often critical in order to prove consumption in clinical and forensic settings. In this research, the metabolite profile of two pyrrolidinyl SCs, α-pyrrolidinohexaphenone (α-PHP) and 4′′-fluoro-α-pyrrolidinovalerophenone (4F-α-PVP), were characterized to identify optimal intake markers. Experiments were conducted using pooled human hepatocyte incubations followed by liquid chromatography–high-resolution tandem mass spectrometry and data-mining software. We suggest α-PHP dihydroxy-pyrrolidinyl, α-PHP hexanol, α-PHP 2′-keto-pyrrolidinyl-hexanol, and α-PHP 2′-keto-pyrrolidinyl as markers of α-PHP use, and 4F-α-PVP dihydroxy-pyrrolidinyl, 4F-α-PVP hexanol, 4F-α-PVP 2′-keto-pyrrolidinyl-hexanol, and 4F-α-PVP 2′-keto-pyrrolidinyl as markers of 4F-α-PVP use. These results represent the first data available on 4F-α-PVP metabolism. The metabolic fate of α-PHP was previously studied using human liver microsomes and urine samples from α-PHP users. We identified an additional major metabolite (α-PHP dihydroxy-pyrrolidinyl) that might be crucial for documenting exposure to α-PHP. Further experiments with suitable analytical standards, which are yet to be synthesized, and authentic specimens should be conducted to confirm these results.
Highlights
Synthetic cathinones (SCs), or bath salts, are novel psychoactive substances (NPSs) designed to induce cocaine-like stimulant effects while evading legislation and analytical detection
4F-α-PVP, we investigated their metabolite fate using pooled human hepatocyte incubations, liquid chromatography–high-resolution tandem mass spectrometry (LC-HRMS/MS), and data-mining software, with the aim of identifying suitable markers of consumption
McLafferty rearrangement through the ionization of the oxygen atom may occur, yielding fragment m/z 70.0652 from α-PHP and 4F-α-PVP. α-PHP fragmentation matches well with that reported by Matsuta et al, the instrument employed was different [35]. 4F-α-PVP
Summary
Synthetic cathinones (SCs), or bath salts, are novel psychoactive substances (NPSs) designed to induce cocaine-like stimulant effects while evading legislation and analytical detection. SCs inhibit the transport of monoamines in the central nervous system, with specific affinities for dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT, respectively), inducing euphoria and increased energy, and tachycardia, elevated blood pressure, hyperthermia, agitation, delirium, psychosis, and death. SC use accounts for many intoxications and deaths, mainly through cardiac arrest or multiorgan failure [1,2]. SC effects are closely related to their specific selectivity for DAT, NET, and SERT. DAT/SERT inhibition is associated with distinct psychoactive effects and abuse liability.
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