Synthesis and analytical differentiation of a novel synthetic cathinone 1-(2,3-dihydro-1H-inden-5-yl)-2-(pyrrolidin-1-yl)butan-1-one (5-PPDI) and its regioisomers

3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) and the most widespread and life-threatening synthetic cathinone of the “bath salts”. Preclinical research has proven the cocaine-like psychostimulant effects of MDPV and its potential for abuse. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid that has emerged as a new potential treatment for drug addiction. Here, we tested the effects of CBD (20 mg/kg) on MDPV (2 mg/kg)-induced conditioned place preference and MDPV (0.05 and 0.075 mg/kg/infusion) self-administration paradigms. In addition, we assessed the effects of the co-administration of CBD and MDPV (3 and 4 mg/kg) on anxiety-like behaviour using the elevated plus maze (EPM). CBD mitigated the MDPV-induced conditioned place preference. On the contrary, CBD administration throughout the MDPV (0.075 mg/kg/infusion) self-administration increased drug-seeking and taking behaviours, but only in the high-responders group of mice. Furthermore, CBD exerted anxiolytic-like effects, exclusively in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice varies depending on the requirements of the learning task, resulting in a complex response. Therefore, further research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed.

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Investigation and Resolution of Interference in the LC-QTOF-MS Detection of 4-MePPP

Journal of Analytical Toxicology ◽

10.1093/jat/bkaa199 ◽

2021 ◽

Author(s):

Darren R Allen ◽

Christopher Warnholtz ◽

Brett C McWhinney

Keyword(s):

Reference Material ◽

Spectral Data ◽

False Positive ◽

In Silico ◽

Spectral Library ◽

In Silico Fragmentation ◽

False Positive Detection ◽

Product Ions ◽

Synthetic Cathinone ◽

Recent Addition

Abstract An interference resulting in the false-positive detection of the synthetic cathinone 4-MePPP in urine was suspected following the recent addition of 4-MePPP spectral data to an LC-QTOF-MS drug library. Although positive detection criteria were achieved, it was noted that all urine samples suspected of containing 4-MePPP also concurrently contained high levels of tramadol and its associated metabolites. Using QTOF-MS software elucidation tools, candidate compounds for the suspected interference were proposed. To provide further confidence in the identity of the interference, in silico fragmentation tools were used to match product ions generated in the analysis with product ions predicted from the theoretical fragmentation of candidate compounds. The ability of the suspected interference to subsequently produce the required product ions for spectral library identification of 4-MePPP was also tested. This information was used to provide a high preliminary confidence in the compound identity prior to purchase and subsequent confirmation with certified reference material. A co-eluting isobaric interference was identified and confirmed as an in-source fragment of the tramadol metabolite, N,N-bisdesmethyltramadol. Proposed resolutions for this interference are also described and subsequently validated by retrospective interrogation of previous cases of suspected interference.

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