Prediction of designer drugs: Synthesis and spectroscopic analysis of synthetic cathinone analogs that may appear on the Swedish drug market

Abstract

The use of hyphenated analytical techniques in forensic drug screening enables simultaneous identification of a wide range of different compounds. However, the appearance of drug seizures containing new substances, mainly new psychoactive substances (NPS), is steadily increasing. These new and other already known substances often possess structural similarities and consequently they exhibit spectral data with slight differences. This situation has made the criteria that ensure indubitable identification of compounds increasingly important. In this work, 6 new synthetic cathinones that have not yet appeared in any Swedish drug seizures were synthesized. Their chemical structures were similar to those of already known cathinone analogs of which 42 were also included in the study. Hence, a total of 48 synthetic cathinones making up sets of homologous and regioisomeric compounds were used to challenge the capabilities of various analytical techniques commonly applied in forensic drug screening, ie, gas chromatography-mass spectrometry (GC-MS), gas chromatography-Fourier transform infrared spectroscopy (GC-FTIR), nuclear magnetic resonance (NMR), and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Special attention was paid to the capabilities of GC-MS and GC-FTIR to distinguish between the synthetic cathinones and the results showed that neither GC-MS nor GC-FTIR alone can successfully differentiate between all synthetic cathinones. However, the 2 techniques proved to be complementary and their combined use is therefore beneficial. For example, the structural homologs were better differentiated by GC-MS, while GC-FTIR performed better for the regioisomers. Further, new spectroscopic data of the synthesized cathinone analogs is hereby presented for the forensic community. The synthetic work also showed that cathinone reference compounds can be produced in few reaction steps.

The clinical challenges of synthetic cathinones

“…Some clients may simply need reassurance, support and medical monitoring. Management of cathinone, and indeed of any NPS/unknown psychotropics’ ingestion, is typically directed at dealing with adverse effects as they arise . Due to the similarity of cathinones with other stimulants, management strategies similar to those recommended for intoxication with those drugs might be useful .…”

“…Agitated adults can be sedated with an initial dose of oral or intravenous diazepam (0.1–0.3 mg/kg body weight). At times, larger doses/frequent re‐dosing to achieve adequate sedative effect may be required . Further targeted treatment to control aggression and agitation may include intramuscular or intranasal midazolam, or intramuscular lorazepam.…”

“…Management of cathinone, and indeed of any NPS/unknown psychotropics' ingestion, is typically directed at dealing with adverse effects as they arise. 83 Due to the similarity of cathinones with other stimulants, management strategies similar to those recommended for intoxication with those drugs might be useful. 84 For example, if a diagnosis of cathinone-induced delirium is suspected, treatment efforts should focus on controlling agitation and then treating medical complications such as metabolic acidosis.…”

“…At times, larger doses/frequent re-dosing to achieve adequate sedative effect may be required. 83,85 Further targeted treatment to control aggression and agitation may include intramuscular or intranasal midazolam, or intramuscular lorazepam. This approach may be useful as well to stop seizures.…”

Tentative identification of the phase I and II metabolites of two synthetic cathinones, MDPHP and α‐PBP, in human urine

“…Gas and liquid chromatography-mass spectrometries are mainly used for the identification of synthetic cathinones including MDPHP and α-PBP in seized and forensic case samples. [11][12][13][14][15] However, the analysis of these compounds in biological specimens (blood, urine, hair, oral fluid, and tissue) is performed mainly by liquid chromatography-tandem mass spectrometry due to the complexities of biological matrices. 13,[16][17][18][19][20][21][22] Due to the relative to non-invasiveness of sample collection and the simplicity of sample preparation, urine is often the preferred biofluid matrix for analytical confirmation of ingestion.…”