• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
LIU Shengfeng, ZHANG Lan, LIU Shucheng, HOU Chenzhi, XU Peng, DI Bin. Phase I metabolism of four amide synthetic cannabinoids in human liver microsomes[J]. Journal of China Pharmaceutical University, 2022, 53(5): 577-590. DOI: 10.11665/j.issn.1000-5048.20220508
Citation: LIU Shengfeng, ZHANG Lan, LIU Shucheng, HOU Chenzhi, XU Peng, DI Bin. Phase I metabolism of four amide synthetic cannabinoids in human liver microsomes[J]. Journal of China Pharmaceutical University, 2022, 53(5): 577-590. DOI: 10.11665/j.issn.1000-5048.20220508
shu

Phase I metabolism of four amide synthetic cannabinoids in human liver microsomes

  • 1.

    Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009

  • 2.

    China National Narcotics Control Commission-China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control, Nanjing 210009

  • 3.

    Key Laboratory of Drug Monitoring and Control, Drug Intelligence and Forensic Center, Ministry of Public Security, Beijing 100193, China

More Information
  • Received Date: March 23, 2022
  • Revised Date: September 13, 2022
    Graphical Abstract
    • Abstract
  • This study was performed to determine the metabolic profile of four amide synthetic cannabinoids that recently abused, i.e., ADB-4en-PINACA, 4CN-CUMYL-BUTINACA, 5F-EMB-PICA and 4F-MDMB-BUTICA, in human liver microsomes (HLMs). The four amide synthetic cannabinoids were added to the microsomal incubation model, being incubated for 10 min, 60 min or 3 h to simulate human hepatic metabolism.Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analytical instrument was employed to determine and speculate the structure of phase I metabolites and their possible metabolic pathways.The results showed that there were 27 phase I metabolic pathways for the four amide synthetic cannabinoids, including hydroxylation, carboxylation, N-dealkylation and ester hydrolysis, with the main phase I metabolic pathways of ester hydrolysis, dihydrodiol (pentenyl tail), oxidative defluorination to carboxylic acid, monohydroxylation (alkyl side chain or indole/indazole ring) and N-dealkylation.The results of this study may provide potential detection markers for forensic identification and sewage abuse assessment of the four amide synthetic cannabinoids.
    • FullText(HTML)
    • References (21)
  • [1]
    . Drug Test Anal，2022，14（2）：307-316.
    [2]
    Yang F，Dong LB，Cai WJ. Detection and analysis of new synthetic cannabinoid in electronic cigarette oil［J］. Chin J Forensic Med（中国法医学杂志），2021，36 （5）：481-482.
    [3]
    Li YY，Ding XQ，Han P. Identifying synthetic Cannabis 5F-ADBICA and 5F-MDMB-PICA in electronic cigarette oil with GC-MS［J］. Guangdong Chem Ind（广东化工），2020（23）：126-127，140.
    [4]
    Thornton MD，Baum CR. Bath salts and other emerging toxins［J］. Pediatr Emerg Care，2014，30（1）：47-52.
    [5]
    Grigg J，Manning V，Arunogiri S，et al. Synthetic cannabinoid use disorder：an update for general psychiatrists［J］. Australas Psychiatry，2019，27（3）：279-283.
    [6]
    Waugh J，Najafi J，Hawkins L，et al. Epidemiology and clinical features of toxicity following recreational use of synthetic cannabinoid receptor agonists：a report from the United Kingdom National Poisons Information Service［J］. Clin Toxicol，2016，54（6）：512-518.
    [7]
    Darke S，Banister S，Farrell M，et al. ‘Synthetic cannabis’：a dangerous misnomer［J］. Int J Drug Policy，2021，98：103396.
    [8]
    Brents LK，Prather PL. The K2/Spice phenomenon：emergence，identification，legislation and metabolic characterization of synthetic cannabinoids in herbal incense products［J］. Drug MeTable Rev，2014，46（1）：72-85.
    [9]
    Li C，Wang JF，Xu DQ，et al. Inspection of phase I metabolites of synthetic cannabinoid JWH-073 in human liver microsomes by ultra high performance liquid chromatography-high resolution mass spectrometry［J］. Phys Test Chem Anal （理化检验 化学分册），2019，55 （8）：869-875.
    [10]
    Presley BC，Castaneto MS，Logan BK，et al. Metabolic profiling of synthetic cannabinoid 5F-ADB and identification of metabolites in authentic human blood samples via human liver microsome incubation and ultra-high-performance liquid chromatography/high-resolution mass spectrometry［J］. Rapid Commun Mass Spectrom，2020，34（22）：e8908.
    [11]
    Watanabe S，Vikingsson S，?strand A，et al. Biotransformation of the new synthetic cannabinoid with an alkene，MDMB-4en-PINACA，by human hepatocytes，human liver microsomes，and human urine and blood［J］. AAPS J，2020，22（1）：13.
    [12]
    Sia CH，Wang ZT，Goh EML，et al. Urinary metabolite biomarkers for the detection of synthetic cannabinoid ADB-BUTINACA abuse［J］. Clin Chem，2021，67（11）：1534-1544.
    [13]
    Norman C，McKirdy B，Walker G，et al. Large-scale evaluation of ion mobility spectrometry for the rapid detection of synthetic cannabinoid receptor agonists in infused papers in prisons［J］. Drug Test Anal，2021，13（3）：644-663.
    [14]
    Li JR，Wang JF，Zhang WF，et al. Metabolic markers of the synthetic cannabinoid 5F-EMB-PICA in zebrafish［J］. Chin J Anal Lab （分析试验室）：1-11.
    [15]
    Kronstrand R，Norman C，Vikingsson S，et al. The metabolism of the synthetic cannabinoids ADB-BUTINACA and ADB-4en-PINACA and their detection in forensic toxicology casework and infused papers seized in prisons［J］. Drug Test Anal，2022，14（4）：634-652.
    [16]
    Wang KD，Yuan XL，Zhang YR，et al. Detection of 4F-MDMB-BICA，a new synthetic cannabinoid psychoactive substance［J］. Chin J Forensic Med（中国法医学杂志），2021，36（1）：25-29.
    [17]
    Yue LN，Xiang P，Shen BH，et al. Metabolism of 4F-MDMB-BICA in zebrafish by liquid chromatography-high resolution mass spectrometry［J］. Drug Test Anal，2021，13（6）：1223-1229.
    [18]
    Ar?kan ?lmez N，Kapucu H，?all? Altun N，et al. Identification of the synthetic cannabinoid N-（2-phenyl-propan-2-yl）-1-（4-cyanobutyl）-1H-indazole-3-carboxamide （CUMYL-4CN-BINACA） in a herbal mixture product［J］.Forensic Toxicol，2018，36（1）：192-199.
    [19]
    Kevin RC，Anderson L，McGregor IS，et al. CUMYL-4CN-BINACA is an efficacious and potent pro-convulsant synthetic cannabinoid receptor agonist［J］. Front Pharmacol，2019，10：595.
    [20]
    ?ztürk YE，Yeter O，?ztürk S，et al. Detection of metabolites of the new synthetic cannabinoid CUMYL-4CN-BINACA in authentic urine samples and human liver microsomes using high-resolution mass spectrometry［J］. Drug Test Anal，2018，10（3）：449-459.
    [21]
    ?strand A，Vikingsson S，Lindstedt D，et al. Metabolism study for CUMYL-4CN-BINACA in human hepatocytes and authentic urine specimens：free cyanide is formed during the main metabolic pathway［J］. Drug Test Anal，2018，10（8）：1270-1279.
    • Related Articles

  • Related Articles

    [1]SHANG Feiyang, LIU Chengbo, TAN Hongzhou, HE Bing, HE Liqin. Design, synthesis and antiplatelet aggregation activity of 3-acetyl-7-hydroxycoumarin derivatives[J]. Journal of China Pharmaceutical University, 2024, 55(3): 367-374. DOI: 10.11665/j.issn.1000-5048.2023072901
    [2]DAI Weiguo, TAN Hongzhou, GU Hongxia, HE Bing, HE Liqin, HUANG Peng. Design, synthesis and anti-platelet aggregation activity of paeonol oxime derivatives[J]. Journal of China Pharmaceutical University, 2022, 53(5): 535-541. DOI: 10.11665/j.issn.1000-5048.20220504
    [3]WANG Xiaoli, WANG Zhaoya, WANG Linna, JI Hui, ZHANG Yihua, YIN Jian. Design, synthesis and evaluation of hydrogen sulfide-releasing derivatives of ring opening 3-n-butylphthalide as novel platelet aggregation inhibitors[J]. Journal of China Pharmaceutical University, 2016, 47(2): 158-162. DOI: 10.11665/j.issn.1000-5048.20160205
    [4]FANG Jiangen, WANG Xuliang, LING Jingjing, YIN Wei, XU Jinyi, JI Hui, ZHANG Yihua. Synthesis and antiplatelet aggregation/antioxidant activity of 3-alkyl-benzo［c］ selenophen-1(3H)-ones[J]. Journal of China Pharmaceutical University, 2015, 46(5): 552-555. DOI: 10.11665/j.issn.1000-5048.20150506
    [5]WU Mingming, FANG Lei, GOU Shaohua, CHEN Li. 以2-甲基-2-取代苯氧基丙酸为离去基团的铂(Ⅱ)配合物的合成、表征及细胞毒活性[J]. Journal of China Pharmaceutical University, 2013, 44(4): 303-306. DOI: 10.11665/j.issn.1000-5048.20130403
    [6]YANG Chunyu, HUANG Zhangjian, LING Jingjing, JI Hui, LAI Yisheng, XU Jinyi, PENG Sixun, ZHANG Yihua. Synthesis and evaluation of carbamate-isosorbide-3-n-butylphthalide ring opening derivative trihybrids as novel platelet aggregation inhibitors[J]. Journal of China Pharmaceutical University, 2013, 44(3): 202-206. DOI: 10.11665/j.issn.1000-5048.20130302
    [7]ZHANG Bo-yu, SHAN Jia-qi, LIU Lin, JIAO Bo, SUN Hong-bin. Synthesis and antiplatelet aggregation activities of prasugrel derivatives[J]. Journal of China Pharmaceutical University, 2011, 42(4): 305-309.
    [8]Synthesis and anti-platelet aggregation activity of substituted (E)-1，2-diarylethene compounds[J]. Journal of China Pharmaceutical University, 2010, 41(5): 419-423.
    [9]LI Bao-quan, LI Nian-guang, FENG Feng, TANG Yu-ping, DUAN Jin-ao. Synthesis and anti-platelet aggregation activities of ferulic acid esters[J]. Journal of China Pharmaceutical University, 2009, 40(6): 486-490.
    [10]Synthesis and Antiplatelet Aggregation of N Acylated Tetrahydrobenzylisoquinoline[J]. Journal of China Pharmaceutical University, 1997, (5): 3+6-7.

Catalog

    Get Citation
    PDF
    XML
    Article views (229) PDF downloads (528) Cited by()
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    Copyright © Journal of China Pharmaceutical University苏ICP备12050101号-2

    Address：24 Tongjia Lane, Nanjing City, Jiangsu Province （210009）Tel: 025-83271566E-mail: xuebao@cpu.edu.cn

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    Total visits：308650

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return