Gas and liquid chromatography–mass spectrometry studies on the metabolism of the synthetic phenylacetylindole cannabimimetic JWH-250, the psychoactive component of smoking mixtures

Grigoryev, Andrej; Мельник, А А; Savchuk, S. A.; Simonov, Anton; Rozhanets, V. V.

doi:10.1016/j.jchromb.2011.07.004

Cited by 73 publications

(64 citation statements)

References 13 publications

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“…Organic solvent percentage (methanol and DMSO, respectively) was <1%. One hundred-microliter samples were collected at 0, 3,8,13,20,30,45, and 60 min and added to 100 μL ice-cold acetonitrile. Samples were centrifuged in a 5804r bench top centrifuge (Eppendorf, Hamburg, Germany) (15,000g, 4°C, 10 min), supernatant was removed and stored at −80°C.…”

Section: Metabolic Stability Assessment With Hlmmentioning

confidence: 99%

“…Further, it is necessary to identify the most prevalent metabolites for synthesis of reference standards for analytical method development. Since the first appearance of synthetic cannabinoids, many metabolism studies with human liver microsomes (HLM), human hepatocytes, and/or authentic specimens elucidated their metabolic pathways (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

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Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA

Wohlfarth

Castaneto

Zhu

et al. 2015

AAPS J

144

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Abstract. Whereas non-fluoropentylindole/indazole synthetic cannabinoids appear to be metabolized preferably at the pentyl chain though without clear preference for one specific position, their 5-fluoro analogs' major metabolites usually are 5-hydroxypentyl and pentanoic acid metabolites. We determined metabolic stability and metabolites of N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and 5-fluoro-AB-PINACA (5F-AB-PINACA), two new synthetic cannabinoids, and investigated if results were similar. In silico prediction was performed with MetaSite (Molecular Discovery). For metabolic stability, 1 μmol/L of each compound was incubated with human liver microsomes for up to 1 h, and for metabolite profiling, 10 μmol/L was incubated with pooled human hepatocytes for up to 3 h. Also, authentic urine specimens from AB-PINACA cases were hydrolyzed and extracted. All samples were analyzed by liquid chromatography high-resolution mass spectrometry on a TripleTOF 5600+ (AB SCIEX) with gradient elution (0.1% formic acid in water and acetonitrile). High-resolution full-scan mass spectrometry (MS) and information-dependent acquisition MS/MS data were analyzed with MetabolitePilot (AB SCIEX) using different data processing algorithms. Both drugs had intermediate clearance. We identified 23 AB-PINACA metabolites, generated by carboxamide hydrolysis, hydroxylation, ketone formation, carboxylation, epoxide formation with subsequent hydrolysis, or reaction combinations. We identified 18 5F-AB-PINACA metabolites, generated by the same biotransformations and oxidative defluorination producing 5-hydroxypentyl and pentanoic acid metabolites shared with AB-PINACA. Authentic urine specimens documented presence of these metabolites. AB-PINACA and 5F-AB-PINACA produced suggested metabolite patterns. AB-PINACA was predominantly hydrolyzed to AB-PINACA carboxylic acid, carbonyl-AB-PINACA, and hydroxypentyl AB-PINACA, likely in 4-position. The most intense 5F-AB-PINACA metabolites were AB-PINACA pentanoic acid and 5-hydroxypentyl-AB-PINACA.

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Section: Metabolic Stability Assessment With Hlmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA

Wohlfarth

Castaneto

Zhu

et al. 2015

AAPS J

144

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“…The metabolism studies of SCs are based on in vivo experiments [40,[43][44][45][46][47][48][49][50][51][52][53] or on in vitro experiments with human or rat liver microsomes [24,41,43,44,[53][54][55][56][57][58][59][60][61][62][63]. Due to the speed of both the emergence and spread of SCs on the world market, the pharmacokinetics properties of some SCs have not been satisfactorily investigated.…”

Section: Pharmacological and Toxicological Aspects Of Synthetic Cannamentioning

confidence: 99%

“…trimethylsilylation [9,46,80,99], methylation [80], acetylation [46,99] or trifluoroacetylation [46,99]. Acetylation is preferred to routine analyses despite the slightly lower sensitivity because trifluoroacetylation can cause low thermal stability for JWH-018, JWH-073, JWH-250 and their metabolites [99].…”

Section: Gas Chromatographymentioning

confidence: 99%

Bioanalytical methods for the determination of synthetic cannabinoids and metabolites in biological specimens

Aldlgan

Torrance

2016

TrAC Trends in Analytical Chemistry

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Recently the use of synthetic cannabinoids (SCs) has increased around the world. As a result, the importance for accurate analysis of SCs in human biological matrices is evident and continues to be especially challenging due to their chemical structures being constantly modified. Many methods have been published recently for the analysis of SCs in human biological samples. This review provides an overview of the analytical methods used for the analysis of SCs and their metabolites in biological specimens with a special focus on chromatographic analysis and sample preparation.Liquid chromatography assay is the most commonly used for confirmation purposes of SCs and their metabolites in biological matrices. In blood and oral fluid, analysis of SCs must be very sensitive. In urine, SCs have extensive metabolism pathways; therefore the main target compounds are their hydroxyl and carboxyl metabolites, which is important to recognise when establishing clinical and forensic toxicology analytical methods.

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“…Furthermore, in hair (and in keratinized matrices in general) parent, un-metabolized drugs accumulate prevalently, in comparison with the corresponding metabolites [13]. Conversely, studies performed both in vivo and in vitro on some of the synthetic cannabinoids showed that they are extensively metabolized, and in many cases no parent compound is detectable in urine [14][15][16][17][18]. Thus, whereas the determination of synthetic cannabinoids in urine and blood will therefore be faced with the issue of identifying several metabolites often not well known, hair analysis can be focussed directly on the parent drug.…”

Section: Introductionmentioning

confidence: 99%

Screening for new psychoactive substances in hair by ultrahigh performance liquid chromatography–electrospray ionization tandem mass spectrometry

Rossi

Odoardi

Fisichella

et al. 2014

Journal of Chromatography A

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Gas and liquid chromatography–mass spectrometry studies on the metabolism of the synthetic phenylacetylindole cannabimimetic JWH-250, the psychoactive component of smoking mixtures

Cited by 73 publications

References 13 publications

Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA

Pentylindole/Pentylindazole Synthetic Cannabinoids and Their 5-Fluoro Analogs Produce Different Primary Metabolites: Metabolite Profiling for AB-PINACA and 5F-AB-PINACA

Bioanalytical methods for the determination of synthetic cannabinoids and metabolites in biological specimens

Screening for new psychoactive substances in hair by ultrahigh performance liquid chromatography–electrospray ionization tandem mass spectrometry

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