Synthetic cannabinoids abused in South Korea: drug identifications by the National Forensic Service from 2009 to June 2013

Chung, Heesun; Choi, Hyeyoung; Heo, Sewoong; Kim, Eun‐Mi; Lee, Jaesin

doi:10.1007/s11419-013-0213-6

Cited by 55 publications

(59 citation statements)

References 18 publications

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“…Another noticeable feature is the increase of fluorinated derivatives as presented in the aforementioned cases. These results are in accordance with a recent report on the trends of synthetic cannabinoids identified in Korea [3].…”

Section: Discussionsupporting

confidence: 93%

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Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry

et al. 2015

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Despite efforts by legal authorities to control the abuse of synthetic cannabinoids, new derivatives have continually emerged on the market to circumvent regulations, and its abuse has become a threat to public health. Thus, development of analytical methods for confirming drug intake in biological fluids is essential to ensure effective drug control and to address further drug intoxication cases. Herein, a sensitive and reliable liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous determination of 37 synthetic cannabinoid metabolites, such as N-hydroxypentyl and carboxy metabolites, using 100 ll of urine. Urine specimens were treated by enzymatic hydrolysis and solid-phase extraction. Limits of detection for the evaluated drugs ranged from 0.1 to 1 ng/ml, and the linear range spanned from 0.25 or 1 to 100 ng/ml. Precision and accuracy bias were 1.4-12.1 % and -7.2-7.2 %, respectively. Matrix effects biases were in the range of 0.4 to 10.1 %, and extraction recoveries were 65-99 %. In addition, all analytes were stable under storage conditions of 4°C and -20°C for 14 days, and after three freeze-thaw cycles. The developed method was successfully applied to actual urine specimens obtained from synthetic cannabinoid users. The present method enabled simultaneous quantification of 37 synthetic cannabinoid metabolites, including their regioisomers, in urine in the field of clinical and forensic toxicology.

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Section: Discussionsupporting

confidence: 93%

“…However, herbal mixtures called ''Spice'' containing synthetic cannabinoids as synthetic additives have gained popularity globally since 2008 [1][2][3][4]. These mixtures are sold at head shops and gas stations and can be accessed via the Internet and even vending machines as incenses or air fresheners.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry

et al. 2015

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“…The N-butyl homologue of RCS-4, RCS-4-C4 (6), was found in products purchased in New Zealand in July 2011 [19], and the regioisomeric RCS-2-C4 (4) was identified in seized products by researchers at the National Forensic Service in South Korea in October 2012 [22]. The same group also found RCS-2 (7) and RCS-3 (8) in their seizure materials until June 2013 [23]. The structures of the homologues of RCS-4, together with JWH-018, CP 47,497, and D 9 -THC are shown in Fig.…”

Section: Introductionmentioning

confidence: 95%

Structure–activity relationships of synthetic cannabinoid designer drug RCS-4 and its regioisomers and C4 homologues

et al. 2015

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-1-yl-(1-pentyl-1H-indol-3-yl)methanone] represents the first of several Nalkyl-3-(methoxybenzoyl)indoles identified by forensic scientists as synthetic cannabinoid (SC) designer drugs. Despite the detection of RCS-4 and several analogues (RCS-2, RCS-3, RCS-2-C4, RCS-3-C4, and RCS-4-C4) in products intended for human consumption, relatively little is known about this class of cannabinoids. The synthesis of all regioisomers of RCS-4 and their C4 homologues is described. This study also systematically explored the structure-activity relationships of this class of SCs at human CB 1 and CB 2 receptors using an in vitro fluorometric imaging plate reader membrane potential assay. All compounds demonstrated agonist activity at CB 1 (EC 50 = 54-574 nM) and CB 2 (EC 50 = 4.5-46 nM) receptors, with the C4 homologues showing a preference for CB 2 receptors over CB 1 receptors (31-42 times). Since most of the analogues (RCS-2, RCS-3, RCS-2-C4, RCS-3-C4 and RCS-4-C4) are not subject to regulation in much of the world, despite their activities towards CB 1 and CB 2 receptors, there is a possibility that these analogues will emerge on the black market.

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“…Structure-activity relationships for synthetic cannabinoids have been established [4][5][6][7][8], and JWH compounds (JWH-018, JWH-122, and JWH-073) have been modified as follows: introduction of a fluorine atom (AM-2201, MAM-2201, and EAM-2201) [9] and substitution of the naphthyl group for a cyclopropyl group (UR-144 and XLR-11) [10,11], adamantyl group (APICA and 5F-APICA) [10], or quinolinyl group (QUPIC and QUCHIC) [12,13]. Synthetic cannabinoids have been found in seized herbal materials, and their continual emergence on recreational and illicit drug markets has become a global issue [14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

et al. 2016

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MAM-2201 is a synthetic cannabinoid that is increasingly found in recreational drug abusers and cases of severe intoxication. Thus, characterization of the metabolic pathways of MAM-2201 is necessary to predict individual pharmacokinetics and toxicity differences, and to avoid toxic drug-drug interactions. Collectively, 19 phase 1 metabolites of MAM-2201 were identified using liquid chromatography-Orbitrap mass spectrometry following human liver microsomal incubations in the presence of NADPH: 7 hydroxy-MAM-2201 (M1-M7), 4 dihydroxy-MAM-2201 (M8-M11), dihydrodiol-MAM-2201 (M12), N-(5-hydroxypentyl)-MAM-2201 (M13), hydroxy-M13 (M14), N-dealkyl-MAM-2201 (M15), 2 hydroxy-M15 (M16, M17), MAM-2201 N-pentanoic acid (M18), and hydroxy-M18 (M19). On the basis of intrinsic clearance values in human liver microsomes, hydroxy-MAM-2201 (M1), N-(5-hydroxypentyl)-MAM-2201 (M13), and hydroxy-M13 (M14) were the major metabolites. Based on an enzyme kinetics study using human cDNA-expressed cytochrome P450 (CYP) enzymes and an immunoinhibition study using selective CYP antibodies in human liver microsomes, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 enzymes were responsible for MAM-2201 metabolism. The CYP3A4 enzyme played a prominent role in MAM-2201 metabolism, and CYP1A2, CYP2B6, CYP2C8, and CYP2C9 enzymes played major roles in the formation of some metabolites. MAM-2201 is extensively metabolized by multiple CYP enzymes, indicating that MAM-2201 and its metabolites should be used as markers of MAM-2201 abuse and toxicity. Graphical abstract In vitro metabolic pathways of MAM-2201 were characterized in human liver microsomes and recombinant CYPs using LC-HRMS analysis. Total 19 phase I metabolites were identified with predominant contribution of CYP3A4.

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Synthetic cannabinoids abused in South Korea: drug identifications by the National Forensic Service from 2009 to June 2013

Cited by 55 publications

References 18 publications

Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry

Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry

Structure–activity relationships of synthetic cannabinoid designer drug RCS-4 and its regioisomers and C4 homologues

Metabolic characterization of (1-(5-fluoropentyl)-1H-indol-3-yl)(4-methyl-1-naphthalenyl)-methanone (MAM-2201) using human liver microsomes and cDNA-overexpressed cytochrome P450 enzymes

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