Simultaneous determination of five naphthoylindole-based synthetic cannabinoids and metabolites and their deposition in human and rat hair

Kim, Jihyun; Park, Yuran; Park, Meejung; Kim, Eun‐Mi; Yang, Wenjun; Baeck, Seungkyung; Lee, Sooyeun; Han, Sheng

doi:10.1016/j.jpba.2014.09.013

Cited by 42 publications

(32 citation statements)

References 22 publications

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“…Incubation of EAM-2201, a structural analogue of MAM-2201, with human liver microsomes formed 39 phase 1 metabolites [33]; however, in vitro metabolism of MAM-2201 in human liver microsomes resulted in only three metabolites, i.e., N-(5-hydroxypentyl)-MAM-2201, N-(4-hydroxyfluoropentyl)-MAM-2201, and MAM-2201 pentanoic acid [27]. Therefore, it is necessary to identify additional in vitro metabolites of MAM-2201 and separate the metabolites with the same molecular ions ([M + H] + ).…”

Section: Introductionmentioning

confidence: 99%

“…MAM-2201 has been detected in recreational users and intoxication cases, when Tae Yeon Kong and Ju-Hyun Kim contributed equally to this work. plasma concentrations ranged from <0.1 to 49 ng/mL, indicating its extensive metabolism [19][20][21][25][26][27]. N-(5-hydroxypentyl)-MAM-2201, N-(4-hydroxyfluoropentyl)-MAM-2201, MAM-2201 pentanoic acid, and dealkyl-MAM-2201 have been identified as the metabolites of MAM-2201 in urine and hair samples from MAM-2201 abusers [27][28][29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

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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“…In spite of the recent development of immunoassays that target synthetic cannabinoids, they are still limited due to insufficient specificity and the continuous emergence of newly modified synthetic cannabinoids [13,14]. Thus, some screening methods employing mass spectrometric techniques have been developed for selective and sensitive detection of synthetic cannabinoids and their metabolites in various biological matrices [15][16][17][18][19].…”

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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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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“…27 Başka bir çalışmada, sentetik kannabinoid olan AM-2201 uygulanan ratlarda pigmente ve pigmente olmayan kıllarda madde dağılımı açısından fark saptanmamıştır. 28 Kannabinoidler bazik yapıda olmadıklarından pigmentasyondan, etkilenmemektedirler. 29 …”

Section: Kilin Pi̇gmentasyonuunclassified

Incorporation of Drug and Substances in Hair

Mutlu¹,

Aşıcıoğlu²

2018

Turkiye Klinikleri J Foren Sci Leg Med

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aç, homojen bir yapıya sahip gibi görünse de aslında oldukça karmaşık olan biyolojisi kısmen anlaşılmıştır.1 Memelilerde saç; protein (%65-95), su (%15-35), lipit (%1-9) ve minerallerden (<%1) oluşan deri eklerinden biridir. Saç şaftında korteksi çevreleyen bir kütikül bulunduğu gibi, bazı saç tiplerinde santral medullayı çevreleyen ilave bir kütikülde bulunmaktadır.2 Saç apokrin, sebase ve ter bezleriyle yakın ilişkide olan cildin A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Saç; ilaç; birikim; kötüye kullanım A AB BS S T TR RA AC CT T In recent years hair has become a fundamental biological specimen, alternative to the usual samples blood and urine, for drug testing in the fields of forensic toxicology, clinical toxicology and clinical chemistry. Analytical results of drugs of abuse in hair provide useful information on chronic drug use. They are valuable to presume the history and severity of individual drug abuse and to provide supplementary information on drug use to facilitate interpretation of urine drug analysis. Hair testing has larger detection window. The sample collection is non-invasive. Another advantage of hair samples is that it can be stored at room temperature and do not need to be analyzed quickly after they are collected. Hair analysis is also used for detection of gestational drug exposure, doping control and detection of alcohol abuse. It has been reported that drugs are incorporated into hair by binding to such intracellular components as melanins, lipids, and proteins. It has been proposed that drugs and substances can enter into hair during at least 3 stages: from the blood during hair formation, from sweat and sebum, and from external environment. The aim of this review is to document and discuss the mechanisms of drug or substance accumulation in hair and its influencing factors, application of hair analysis.

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Simultaneous determination of five naphthoylindole-based synthetic cannabinoids and metabolites and their deposition in human and rat hair

Cited by 42 publications

References 22 publications

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

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

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

Incorporation of Drug and Substances in Hair

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