Study of the in vitro and in vivo metabolism of 4-HO-MET
•in vitro and in vivo metabolism of 4-HO-MET.•12 in vitro metabolites.•4 in vivo metabolites.•Hydroxylation, carboxylation, deamination and glucuronidation. 4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET) is a new psychoactive substance (NPS) of the chemical class of tryptamines. It shows structural...
Gespeichert in:
| Veröffentlicht in: | Forensic science international 2018-09, Vol.290, p.103-110 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 110 |
|---|---|
| container_issue | |
| container_start_page | 103 |
| container_title | Forensic science international |
| container_volume | 290 |
| creator | Bruni, Pia Simona Grafinger, Katharina Elisabeth Nussbaumer, Susanne König, Stefan Schürch, Stefan Weinmann, Wolfgang |
| description | •in vitro and in vivo metabolism of 4-HO-MET.•12 in vitro metabolites.•4 in vivo metabolites.•Hydroxylation, carboxylation, deamination and glucuronidation.
4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET) is a new psychoactive substance (NPS) of the chemical class of tryptamines. It shows structural similarities to the endogenous neurotransmitter serotonin, and is a serotonergic hallucinogen, affecting emotional, motoric, and cognitive functions. The knowledge about its biotransformation is mandatory to confirm the abuse of the substance by urine analysis in forensic cases. Therefore, phase I metabolites were generated by the use of the pooled human liver microsomes (pHLM) in vitro model and analyzed by high-performance liquid chromatography high-resolution tandem mass spectrometry with information-dependent acquisition (HPLC-IDA-HR-MS/MS). Furthermore, three authentic urine samples was analyzed and results were compared: 12 different in vitro and 4 in vivo metabolites were found. The predominant biotransformation steps observed in vitro were mono- or dihydroxylation of 4-HO-MET, besides demethylation, demethylation in combination with monohydroxylation, formation of a carboxylic acid, deethylation, and oxidative deamination. In vivo, monohydroxylation, and glucuronidation were detected. A metabolic pathway based on these results was proposed.
For the analysis of urine samples in forensic cases, the N-oxide metabolite and the HO-alkyl metabolite are recommended as target compounds, besides the glucuronides of 4-HO-MET and the parent compound 4-HO-MET itself. |
| doi_str_mv | 10.1016/j.forsciint.2018.06.037 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2071565488</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0379073818303621</els_id><sourcerecordid>2071565488</sourcerecordid><originalsourceid>FETCH-LOGICAL-c399t-23b5654d5eda71d463ba5b6303855ff65df20b404082caacc0e7a890f340b5ef3</originalsourceid><addsrcrecordid>eNqFkE1r3DAQhkVpSDYff6E19JKL3ZFkffi4LNukkJJDkrOQ9UG1rK1Ushfy7yuzyR566WmY4Zl3hgehrxgaDJh_3zU-pmxCGKeGAJYN8Aao-IRWWApScyLpZ7Qqk64GQeUFusx5BwCMEX6OLigAZkS0KySfptm-VdFX029XhbE6hCnFSo_22BxiNbhJ93Ef8rBgbX3_WP_aPl-jM6_32d281yv08mP7vLmvHx7vfm7WD7WhXTfVhPaMs9YyZ7XAtuW016znFKhkzHvOrCfQt9CCJEZrY8AJLTvwtIWeOU-v0O0x9zXFP7PLkxpCNm6_16OLc1YEBF4uSFnQb_-guzinsXxXqI63QmCyUOJImRRzTs6r1xQGnd4UBrXIVTt1kqsWuQq4KirL5pf3_LkfnD3tfdgswPoIuCLkEFxSJcWNxtmQnJmUjeG_R_4C8giMWA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2096477128</pqid></control><display><type>article</type><title>Study of the in vitro and in vivo metabolism of 4-HO-MET</title><source>Elsevier ScienceDirect Journals</source><creator>Bruni, Pia Simona ; Grafinger, Katharina Elisabeth ; Nussbaumer, Susanne ; König, Stefan ; Schürch, Stefan ; Weinmann, Wolfgang</creator><creatorcontrib>Bruni, Pia Simona ; Grafinger, Katharina Elisabeth ; Nussbaumer, Susanne ; König, Stefan ; Schürch, Stefan ; Weinmann, Wolfgang</creatorcontrib><description>•in vitro and in vivo metabolism of 4-HO-MET.•12 in vitro metabolites.•4 in vivo metabolites.•Hydroxylation, carboxylation, deamination and glucuronidation.
4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET) is a new psychoactive substance (NPS) of the chemical class of tryptamines. It shows structural similarities to the endogenous neurotransmitter serotonin, and is a serotonergic hallucinogen, affecting emotional, motoric, and cognitive functions. The knowledge about its biotransformation is mandatory to confirm the abuse of the substance by urine analysis in forensic cases. Therefore, phase I metabolites were generated by the use of the pooled human liver microsomes (pHLM) in vitro model and analyzed by high-performance liquid chromatography high-resolution tandem mass spectrometry with information-dependent acquisition (HPLC-IDA-HR-MS/MS). Furthermore, three authentic urine samples was analyzed and results were compared: 12 different in vitro and 4 in vivo metabolites were found. The predominant biotransformation steps observed in vitro were mono- or dihydroxylation of 4-HO-MET, besides demethylation, demethylation in combination with monohydroxylation, formation of a carboxylic acid, deethylation, and oxidative deamination. In vivo, monohydroxylation, and glucuronidation were detected. A metabolic pathway based on these results was proposed.
For the analysis of urine samples in forensic cases, the N-oxide metabolite and the HO-alkyl metabolite are recommended as target compounds, besides the glucuronides of 4-HO-MET and the parent compound 4-HO-MET itself.</description><identifier>ISSN: 0379-0738</identifier><identifier>EISSN: 1872-6283</identifier><identifier>DOI: 10.1016/j.forsciint.2018.06.037</identifier><identifier>PMID: 30015274</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>4-HO-MET ; Biomarkers ; Biotransformation ; Carboxylic acids ; Cognitive ability ; Conflicts of interest ; Deamination ; Demethylation ; Drug abuse ; Forensic chemistry ; Forensic engineering ; Forensic medicine ; Forensic science ; Forensic sciences ; High performance liquid chromatography ; HPLC-IDA-HR-MS/MS ; Human liver microsomes ; In vivo methods and tests ; Laboratories ; Liquid chromatography ; Liver ; LSD ; Lysergic acid diethylamide ; Mass spectrometry ; Mass spectroscopy ; Metabolism ; Metabolites ; Microsomes ; Narcotics ; NPS ; Organic chemistry ; Potassium ; Psychotropic drugs ; Serotonin ; Synthetic tryptamine ; Tryptamines ; Urine</subject><ispartof>Forensic science international, 2018-09, Vol.290, p.103-110</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier Limited Sep 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-23b5654d5eda71d463ba5b6303855ff65df20b404082caacc0e7a890f340b5ef3</citedby><cites>FETCH-LOGICAL-c399t-23b5654d5eda71d463ba5b6303855ff65df20b404082caacc0e7a890f340b5ef3</cites><orcidid>0000-0002-3647-7455 ; 0000-0001-8659-1304</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0379073818303621$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30015274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bruni, Pia Simona</creatorcontrib><creatorcontrib>Grafinger, Katharina Elisabeth</creatorcontrib><creatorcontrib>Nussbaumer, Susanne</creatorcontrib><creatorcontrib>König, Stefan</creatorcontrib><creatorcontrib>Schürch, Stefan</creatorcontrib><creatorcontrib>Weinmann, Wolfgang</creatorcontrib><title>Study of the in vitro and in vivo metabolism of 4-HO-MET</title><title>Forensic science international</title><addtitle>Forensic Sci Int</addtitle><description>•in vitro and in vivo metabolism of 4-HO-MET.•12 in vitro metabolites.•4 in vivo metabolites.•Hydroxylation, carboxylation, deamination and glucuronidation.
4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET) is a new psychoactive substance (NPS) of the chemical class of tryptamines. It shows structural similarities to the endogenous neurotransmitter serotonin, and is a serotonergic hallucinogen, affecting emotional, motoric, and cognitive functions. The knowledge about its biotransformation is mandatory to confirm the abuse of the substance by urine analysis in forensic cases. Therefore, phase I metabolites were generated by the use of the pooled human liver microsomes (pHLM) in vitro model and analyzed by high-performance liquid chromatography high-resolution tandem mass spectrometry with information-dependent acquisition (HPLC-IDA-HR-MS/MS). Furthermore, three authentic urine samples was analyzed and results were compared: 12 different in vitro and 4 in vivo metabolites were found. The predominant biotransformation steps observed in vitro were mono- or dihydroxylation of 4-HO-MET, besides demethylation, demethylation in combination with monohydroxylation, formation of a carboxylic acid, deethylation, and oxidative deamination. In vivo, monohydroxylation, and glucuronidation were detected. A metabolic pathway based on these results was proposed.
For the analysis of urine samples in forensic cases, the N-oxide metabolite and the HO-alkyl metabolite are recommended as target compounds, besides the glucuronides of 4-HO-MET and the parent compound 4-HO-MET itself.</description><subject>4-HO-MET</subject><subject>Biomarkers</subject><subject>Biotransformation</subject><subject>Carboxylic acids</subject><subject>Cognitive ability</subject><subject>Conflicts of interest</subject><subject>Deamination</subject><subject>Demethylation</subject><subject>Drug abuse</subject><subject>Forensic chemistry</subject><subject>Forensic engineering</subject><subject>Forensic medicine</subject><subject>Forensic science</subject><subject>Forensic sciences</subject><subject>High performance liquid chromatography</subject><subject>HPLC-IDA-HR-MS/MS</subject><subject>Human liver microsomes</subject><subject>In vivo methods and tests</subject><subject>Laboratories</subject><subject>Liquid chromatography</subject><subject>Liver</subject><subject>LSD</subject><subject>Lysergic acid diethylamide</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Microsomes</subject><subject>Narcotics</subject><subject>NPS</subject><subject>Organic chemistry</subject><subject>Potassium</subject><subject>Psychotropic drugs</subject><subject>Serotonin</subject><subject>Synthetic tryptamine</subject><subject>Tryptamines</subject><subject>Urine</subject><issn>0379-0738</issn><issn>1872-6283</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkE1r3DAQhkVpSDYff6E19JKL3ZFkffi4LNukkJJDkrOQ9UG1rK1Ushfy7yuzyR566WmY4Zl3hgehrxgaDJh_3zU-pmxCGKeGAJYN8Aao-IRWWApScyLpZ7Qqk64GQeUFusx5BwCMEX6OLigAZkS0KySfptm-VdFX029XhbE6hCnFSo_22BxiNbhJ93Ef8rBgbX3_WP_aPl-jM6_32d281yv08mP7vLmvHx7vfm7WD7WhXTfVhPaMs9YyZ7XAtuW016znFKhkzHvOrCfQt9CCJEZrY8AJLTvwtIWeOU-v0O0x9zXFP7PLkxpCNm6_16OLc1YEBF4uSFnQb_-guzinsXxXqI63QmCyUOJImRRzTs6r1xQGnd4UBrXIVTt1kqsWuQq4KirL5pf3_LkfnD3tfdgswPoIuCLkEFxSJcWNxtmQnJmUjeG_R_4C8giMWA</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Bruni, Pia Simona</creator><creator>Grafinger, Katharina Elisabeth</creator><creator>Nussbaumer, Susanne</creator><creator>König, Stefan</creator><creator>Schürch, Stefan</creator><creator>Weinmann, Wolfgang</creator><general>Elsevier B.V</general><general>Elsevier Limited</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3647-7455</orcidid><orcidid>https://orcid.org/0000-0001-8659-1304</orcidid></search><sort><creationdate>20180901</creationdate><title>Study of the in vitro and in vivo metabolism of 4-HO-MET</title><author>Bruni, Pia Simona ; Grafinger, Katharina Elisabeth ; Nussbaumer, Susanne ; König, Stefan ; Schürch, Stefan ; Weinmann, Wolfgang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-23b5654d5eda71d463ba5b6303855ff65df20b404082caacc0e7a890f340b5ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>4-HO-MET</topic><topic>Biomarkers</topic><topic>Biotransformation</topic><topic>Carboxylic acids</topic><topic>Cognitive ability</topic><topic>Conflicts of interest</topic><topic>Deamination</topic><topic>Demethylation</topic><topic>Drug abuse</topic><topic>Forensic chemistry</topic><topic>Forensic engineering</topic><topic>Forensic medicine</topic><topic>Forensic science</topic><topic>Forensic sciences</topic><topic>High performance liquid chromatography</topic><topic>HPLC-IDA-HR-MS/MS</topic><topic>Human liver microsomes</topic><topic>In vivo methods and tests</topic><topic>Laboratories</topic><topic>Liquid chromatography</topic><topic>Liver</topic><topic>LSD</topic><topic>Lysergic acid diethylamide</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Microsomes</topic><topic>Narcotics</topic><topic>NPS</topic><topic>Organic chemistry</topic><topic>Potassium</topic><topic>Psychotropic drugs</topic><topic>Serotonin</topic><topic>Synthetic tryptamine</topic><topic>Tryptamines</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bruni, Pia Simona</creatorcontrib><creatorcontrib>Grafinger, Katharina Elisabeth</creatorcontrib><creatorcontrib>Nussbaumer, Susanne</creatorcontrib><creatorcontrib>König, Stefan</creatorcontrib><creatorcontrib>Schürch, Stefan</creatorcontrib><creatorcontrib>Weinmann, Wolfgang</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Forensic science international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bruni, Pia Simona</au><au>Grafinger, Katharina Elisabeth</au><au>Nussbaumer, Susanne</au><au>König, Stefan</au><au>Schürch, Stefan</au><au>Weinmann, Wolfgang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Study of the in vitro and in vivo metabolism of 4-HO-MET</atitle><jtitle>Forensic science international</jtitle><addtitle>Forensic Sci Int</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>290</volume><spage>103</spage><epage>110</epage><pages>103-110</pages><issn>0379-0738</issn><eissn>1872-6283</eissn><abstract>•in vitro and in vivo metabolism of 4-HO-MET.•12 in vitro metabolites.•4 in vivo metabolites.•Hydroxylation, carboxylation, deamination and glucuronidation.
4-Hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET) is a new psychoactive substance (NPS) of the chemical class of tryptamines. It shows structural similarities to the endogenous neurotransmitter serotonin, and is a serotonergic hallucinogen, affecting emotional, motoric, and cognitive functions. The knowledge about its biotransformation is mandatory to confirm the abuse of the substance by urine analysis in forensic cases. Therefore, phase I metabolites were generated by the use of the pooled human liver microsomes (pHLM) in vitro model and analyzed by high-performance liquid chromatography high-resolution tandem mass spectrometry with information-dependent acquisition (HPLC-IDA-HR-MS/MS). Furthermore, three authentic urine samples was analyzed and results were compared: 12 different in vitro and 4 in vivo metabolites were found. The predominant biotransformation steps observed in vitro were mono- or dihydroxylation of 4-HO-MET, besides demethylation, demethylation in combination with monohydroxylation, formation of a carboxylic acid, deethylation, and oxidative deamination. In vivo, monohydroxylation, and glucuronidation were detected. A metabolic pathway based on these results was proposed.
For the analysis of urine samples in forensic cases, the N-oxide metabolite and the HO-alkyl metabolite are recommended as target compounds, besides the glucuronides of 4-HO-MET and the parent compound 4-HO-MET itself.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>30015274</pmid><doi>10.1016/j.forsciint.2018.06.037</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-3647-7455</orcidid><orcidid>https://orcid.org/0000-0001-8659-1304</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0379-0738 |
| ispartof | Forensic science international, 2018-09, Vol.290, p.103-110 |
| issn | 0379-0738 1872-6283 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2071565488 |
| source | Elsevier ScienceDirect Journals |
| subjects | 4-HO-MET Biomarkers Biotransformation Carboxylic acids Cognitive ability Conflicts of interest Deamination Demethylation Drug abuse Forensic chemistry Forensic engineering Forensic medicine Forensic science Forensic sciences High performance liquid chromatography HPLC-IDA-HR-MS/MS Human liver microsomes In vivo methods and tests Laboratories Liquid chromatography Liver LSD Lysergic acid diethylamide Mass spectrometry Mass spectroscopy Metabolism Metabolites Microsomes Narcotics NPS Organic chemistry Potassium Psychotropic drugs Serotonin Synthetic tryptamine Tryptamines Urine |
| title | Study of the in vitro and in vivo metabolism of 4-HO-MET |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T15%3A39%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Study%20of%20the%20in%20vitro%20and%20in%20vivo%20metabolism%20of%204-HO-MET&rft.jtitle=Forensic%20science%20international&rft.au=Bruni,%20Pia%20Simona&rft.date=2018-09-01&rft.volume=290&rft.spage=103&rft.epage=110&rft.pages=103-110&rft.issn=0379-0738&rft.eissn=1872-6283&rft_id=info:doi/10.1016/j.forsciint.2018.06.037&rft_dat=%3Cproquest_cross%3E2071565488%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2096477128&rft_id=info:pmid/30015274&rft_els_id=S0379073818303621&rfr_iscdi=true |