Toxicological investigation of forensic cases related to the designer drug 3,4-methylenedioxypyrovalerone (MDPV): Detection, quantification and studies on human metabolism by GC–MS

Grapp, Marcel; Kaufmann, Christoph; Ebbecke, Martin

doi:10.1016/j.forsciint.2017.01.021

Cited by 38 publications

(18 citation statements)

References 36 publications

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“…This corresponds to a range of 0.014 to 0.29 mg/kg dose in a 70 kg individual. The range of racemic MDPV serum concentrations found in human samples from forensic and intoxicated patients is about 1–1500 ng/ml (Beck et al, 2015; Grapp et al, 2017; Spiller et al, 2011). The concentrations found in our rats after 1 – 5.6 mg/kg iv doses ranged from 2–6932 ng/ml.…”

Section: Discussionmentioning

confidence: 99%

The pharmacokinetics of racemic MDPV and its (R) and (S) enantiomers in female and male rats

Hambuchen

Hendrickson

Gunnell

et al. 2017

Drug and Alcohol Dependence

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Background These studies investigated the serum pharmacokinetic (PK) profile of racemic (3,4)-methylenedioxypyrovalerone [(R,S)-MDPV)] and its (R)- and (S)-enantiomers in female and male Sprague Dawley rats. Methods Intravenous (R,S)-MDPV (3 and 5.6 mg/kg) and single enantiomer of (R)- and (S)-MDPV (1.5 mg/kg) were administered to both sexes for PK studies. Intraperitoneal (ip) bioavailability was determined at 3 mg/kg (R,S)-MDPV. Locomotor activity studies were conducted after ip treatment with saline and 0.3–5.6 mg/kg of (R,S)-MDPV. Results PK values after iv (R,S)-MDPV showed a significant (p<0.05) sex-dependent differences in the volume of distribution at steady state (Vdss) for (R)- and (R,S)-MDPV at both (R,S)-MDPV doses. The female S/R enantiomeric ratios for area under the concentration time curve (AUCinf) and clearance were significantly lower and higher, respectively, than values determined in males. Importantly, there was no evidence of in vivo inversion of (R)-MDPV or (S)-MDPV to its antipode. There were, however, significant sex-dependent differences in volume of distribution after administration of the (R)-enantiomer. Bioavailability studies of ip (R,S)-MDPV showed greater variability and significantly greater bioavailability in male rats. Accordingly, there was a significantly greater maximal distance traveled measurement in male rats at a 3.0 mg/kg dose. Conclusion PK sex differences in (R,S)-MDPV and enantiomers were most apparent in volume of distribution, which could be caused by differences in drug blood and tissue protein binding. The increased magnitude and variance in ip bioavailability in male compared to female rats could lead to sex-dependent differences in the pharmacological action caused by active enantiomer (S)-MDPV.

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Section: Discussionmentioning

confidence: 99%

The pharmacokinetics of racemic MDPV and its (R) and (S) enantiomers in female and male rats

Hambuchen

Hendrickson

Gunnell

et al. 2017

Drug and Alcohol Dependence

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“…In 2017, WADA's Prohibited List sustained the existence of 2 groups of stimulants namely non‐specified and specified compounds. Of note, despite the ever‐growing plethora of “designer” psychoactive substances (including psychostimulants), which have urged forensics and toxicology laboratories to continuously refine testing capabilities, the frequency at which such designer compounds are determined in doping controls is still comparably low.…”

Section: Stimulants Narcotics Cannabinoids and Glucocorticoidsmentioning

confidence: 99%

Annual banned‐substance review: Analytical approaches in human sports drug testing

Thevis

Kuuranne

Geyer

2017

Drug Testing and Analysis

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Several high-profile revelations concerning anti-doping rule violations over the past 12 months have outlined the importance of tackling prevailing challenges and reducing the limitations of the current anti-doping system. At this time, the necessity to enhance, expand, and improve analytical test methods in response to the substances outlined in the World Anti-Doping Agency's (WADA) Prohibited List represents an increasingly crucial task for modern sports drug-testing programs. The ability to improve analytical testing methods often relies on the expedient application of novel information regarding superior target analytes for sports drug-testing assays, drug elimination profiles, alternative test matrices, together with recent advances in instrumental developments. This annual banned-substance review evaluates literature published between October 2016 and September 2017 offering an in-depth evaluation of developments in these arenas and their potential application to substances reported in WADA's 2017 Prohibited List.

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“…Described sample pre‐treatments for urine consist of conventional liquid–liquid extraction (LLE), dispersive liquid–liquid microextraction (DLLME) and SPE, with and without enzymatic hydrolysis (use of β‐glucuronidase) for total cathinones and free cathinones, respectively; although direct determination after protein precipitation and QuEChERS have also been proposed . Recent proposals also perform direct determination (chromatographic injection) after protein separation by centrifugation, enzymatic hydrolysis and centrifugation, conventional (available commercial cartridges) SPE, and LLE . Finally, solid‐phase microextraction (SPME), and volumetric absorptive microsampling (VAMS) have been also used for cathinones assessment in urine.…”

Section: Introductionmentioning

confidence: 99%

“…24 Recent proposals also perform direct determination (chromatographic injection) after protein separation by centrifugation, 26-28 enzymatic hydrolysis and centrifugation, 29,30 conventional (available commercial cartridges) SPE, [31][32][33][34][35] and LLE. [36][37][38][39][40][41][42] Finally, solid-phase microextraction (SPME), 43 and volumetric absorptive microsampling (VAMS) 44 have been also used for cathinones assessment in urine. Some of these developments deal with the assessment of a specific synthetic cathinone, such as 3,4-dimethylmethcathinone (3,4-DMMC), 29 4′-methyl-α-pyrrolidinohexanophenone (MPHP), 27 3,4methylenedioxypyrovalerone (MDPV), 41 mephedrone, 42 and metabolic profiles regarding pyrrolidinohexiophenone (α-PHP), 39 1-phenyl-2-(1-pyrrolidinyl)-1-heptanone (PV8), 34 and 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PVP).…”

Section: Introductionmentioning

confidence: 99%

“…[36][37][38][39][40][41][42] Finally, solid-phase microextraction (SPME), 43 and volumetric absorptive microsampling (VAMS) 44 have been also used for cathinones assessment in urine. Some of these developments deal with the assessment of a specific synthetic cathinone, such as 3,4-dimethylmethcathinone (3,4-DMMC), 29 4′-methyl-α-pyrrolidinohexanophenone (MPHP), 27 3,4methylenedioxypyrovalerone (MDPV), 41 mephedrone, 42 and metabolic profiles regarding pyrrolidinohexiophenone (α-PHP), 39 1-phenyl-2-(1-pyrrolidinyl)-1-heptanone (PV8), 34 and 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (α-PVP). 40 However, appealing methodologies should be applicable to the simultaneous extraction of synthetic cathinones.…”

Section: Introductionmentioning

confidence: 99%

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HPLC‐MS/MS combined with membrane‐protected molecularly imprinted polymer micro‐solid‐phase extraction for synthetic cathinones monitoring in urine

Sánchez–González

Odoardi

Bermejo

et al. 2018

Drug Testing and Analysis

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Synthetic cathinones are a type of drug belonging to group of new psychoactive substances (NPSs). The illicit market for these substances is characterized by the continuous introduction to the market of new analogs to evade legislation and to avoid detection. New screening and confirmation assays are therefore needed, mainly in forensic/clinical samples. In the current development, a porous membrane-protected, micro-solid-phase extraction (μ-SPE) has been developed for the assessment of several cathinones in urine. The μ-SPE device consisted of a cone-shaped polypropylene (PP) porous membrane containing the adsorbent (molecularly imprinted polymers, MIPs, synthesized for the first time for this class of drugs). MIPs were prepared using ethylone and 3-methylmethcathinone (3-MMC) as templates, ethylene glycol dimethacrylate (EGDMA) as a functional monomer, divinylbenzene (DVB) as a cross-linker, and 2,2´-azobisisobutyronitrile (AIBN) as an initiator. The prepared ethylone-based MIP and 3-MMC-based MIP have been fully characterized and evaluated as new selective adsorbents for μ-SPE. Cathinones separation/determination was performed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Optimum loading conditions (pH 5.0, loading for 4.0 minutes under orbital-horizontal shaking at 200 rpm) and elution conditions [2.0 mL of 75:20:5 heptane/2-propanol/ammonium hydroxide and ultrasounds assistance (37 kHz, 325 W) for 4.0 minutes] were found for ethylone-based MIP. Validation (intra-day and inter-day precision and analytical recovery) showed RSD values lower than 9 and 10% for intra-day and inter-day precision, and within the 88%-101% range for intra-day and inter-day analytical recovery.

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Toxicological investigation of forensic cases related to the designer drug 3,4-methylenedioxypyrovalerone (MDPV): Detection, quantification and studies on human metabolism by GC–MS

Cited by 38 publications

References 36 publications

The pharmacokinetics of racemic MDPV and its (R) and (S) enantiomers in female and male rats

The pharmacokinetics of racemic MDPV and its (R) and (S) enantiomers in female and male rats

Annual banned‐substance review: Analytical approaches in human sports drug testing

HPLC‐MS/MS combined with membrane‐protected molecularly imprinted polymer micro‐solid‐phase extraction for synthetic cathinones monitoring in urine

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