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N-Ethyl Pentylone (Ephylone) Intoxications: Quantitative Confirmation and Metabolite Identification in Authentic Human Biological Specimens
N-ethyl pentylone (ephylone) has been identified as the most recent novel stimulant to emerge into the arena of evolving novel psychoactive substances (NPS). Due to its novelty, information regarding case reports with associated quantitative confirmations, biotransformation pathways, and identified...
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Published in: | Journal of analytical toxicology 2018-09, Vol.42 (7), p.467-475 |
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description | N-ethyl pentylone (ephylone) has been identified as the most recent novel stimulant to emerge into the arena of evolving novel psychoactive substances (NPS). Due to its novelty, information regarding case reports with associated quantitative confirmations, biotransformation pathways, and identified unique metabolites will assist the scientific community in understanding the implications of the emergence and risks associated with N-ethyl pentylone use. Authentic blood specimens (n = 26) submitted as part of toxicological death investigations or drugged driving casework tested positive for N-ethyl pentylone, and were quantitatively analyzed by liquid chromatography tandem mass spectrometry (LC-MS-MS). N-ethyl pentylone concentrations ranged from 12 to 1,200 ng/mL, with mean (±standard deviation) and median concentrations of 313 (±366) and 125 ng/mL, respectively, excluding one case measured at 50,000 ng/mL. N-ethyl pentylone was often found in combination with other drugs of abuse and NPS, include a variety of novel opioids including fentanyl analogs. Oral fluid specimens (n = 5), collected from recreational drug users at a dance music festival, were quantitatively analyzed using LC-MS-MS. Concentrations ranged from 12.6 to 1,377 ng/mL. Additional analysis was performed to characterize the metabolic profile of N-ethyl pentylone using human liver microsomes (HLM), followed by confirmation of the presence of the proposed metabolites in a subset of the blood specimens and oral fluid specimens. Metabolomic analysis was performed using a liquid chromatograph quadrupole time-of-flight mass spectrometer (LC-QTOF), followed by data processing using MetabolitePilot™ software. In vivo verification of in vitro HLM-generated metabolites resulted in the confirmation of four metabolites. Reduction of the beta-ketone to an alcohol resulted in the most prominent metabolite found in the authentic specimens, and its uniqueness to N-ethyl pentylone leads to this metabolite being an appropriate biomarker to determine N-ethyl pentylone ingestion. This is the first study to report N-ethyl pentylone concentrations and to characterize the metabolic profile of N-ethyl pentylone. |
doi_str_mv | 10.1093/jat/bky025 |
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Due to its novelty, information regarding case reports with associated quantitative confirmations, biotransformation pathways, and identified unique metabolites will assist the scientific community in understanding the implications of the emergence and risks associated with N-ethyl pentylone use. Authentic blood specimens (n = 26) submitted as part of toxicological death investigations or drugged driving casework tested positive for N-ethyl pentylone, and were quantitatively analyzed by liquid chromatography tandem mass spectrometry (LC-MS-MS). N-ethyl pentylone concentrations ranged from 12 to 1,200 ng/mL, with mean (±standard deviation) and median concentrations of 313 (±366) and 125 ng/mL, respectively, excluding one case measured at 50,000 ng/mL. N-ethyl pentylone was often found in combination with other drugs of abuse and NPS, include a variety of novel opioids including fentanyl analogs. Oral fluid specimens (n = 5), collected from recreational drug users at a dance music festival, were quantitatively analyzed using LC-MS-MS. Concentrations ranged from 12.6 to 1,377 ng/mL. Additional analysis was performed to characterize the metabolic profile of N-ethyl pentylone using human liver microsomes (HLM), followed by confirmation of the presence of the proposed metabolites in a subset of the blood specimens and oral fluid specimens. Metabolomic analysis was performed using a liquid chromatograph quadrupole time-of-flight mass spectrometer (LC-QTOF), followed by data processing using MetabolitePilot™ software. In vivo verification of in vitro HLM-generated metabolites resulted in the confirmation of four metabolites. Reduction of the beta-ketone to an alcohol resulted in the most prominent metabolite found in the authentic specimens, and its uniqueness to N-ethyl pentylone leads to this metabolite being an appropriate biomarker to determine N-ethyl pentylone ingestion. This is the first study to report N-ethyl pentylone concentrations and to characterize the metabolic profile of N-ethyl pentylone.</description><identifier>ISSN: 0146-4760</identifier><identifier>EISSN: 1945-2403</identifier><identifier>DOI: 10.1093/jat/bky025</identifier><identifier>PMID: 29618077</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; Benzodioxoles - blood ; Benzodioxoles - poisoning ; Biotransformation ; Butylamines - blood ; Butylamines - poisoning ; Cause of Death ; Chromatography, Liquid - methods ; Drug Overdose - blood ; Drug Overdose - diagnosis ; Female ; Forensic Toxicology - methods ; Humans ; Male ; Metabolomics - methods ; Microsomes, Liver - metabolism ; Middle Aged ; Psychotropic Drugs - blood ; Psychotropic Drugs - poisoning ; Reproducibility of Results ; Saliva - metabolism ; Substance Abuse Detection - methods ; Tandem Mass Spectrometry ; Young Adult</subject><ispartof>Journal of analytical toxicology, 2018-09, Vol.42 (7), p.467-475</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c323t-fb9753e875ccbe31cdb43fc366b1fa8b78108a3c8922b0732e96f80dd0bb5f6d3</citedby><cites>FETCH-LOGICAL-c323t-fb9753e875ccbe31cdb43fc366b1fa8b78108a3c8922b0732e96f80dd0bb5f6d3</cites><orcidid>0000-0003-1775-1882</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29618077$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krotulski, Alex J</creatorcontrib><creatorcontrib>Papsun, Donna M</creatorcontrib><creatorcontrib>De Martinis, Bruno S</creatorcontrib><creatorcontrib>Mohr, Amanda L A</creatorcontrib><creatorcontrib>Logan, Barry K</creatorcontrib><title>N-Ethyl Pentylone (Ephylone) Intoxications: Quantitative Confirmation and Metabolite Identification in Authentic Human Biological Specimens</title><title>Journal of analytical toxicology</title><addtitle>J Anal Toxicol</addtitle><description>N-ethyl pentylone (ephylone) has been identified as the most recent novel stimulant to emerge into the arena of evolving novel psychoactive substances (NPS). Due to its novelty, information regarding case reports with associated quantitative confirmations, biotransformation pathways, and identified unique metabolites will assist the scientific community in understanding the implications of the emergence and risks associated with N-ethyl pentylone use. Authentic blood specimens (n = 26) submitted as part of toxicological death investigations or drugged driving casework tested positive for N-ethyl pentylone, and were quantitatively analyzed by liquid chromatography tandem mass spectrometry (LC-MS-MS). N-ethyl pentylone concentrations ranged from 12 to 1,200 ng/mL, with mean (±standard deviation) and median concentrations of 313 (±366) and 125 ng/mL, respectively, excluding one case measured at 50,000 ng/mL. N-ethyl pentylone was often found in combination with other drugs of abuse and NPS, include a variety of novel opioids including fentanyl analogs. Oral fluid specimens (n = 5), collected from recreational drug users at a dance music festival, were quantitatively analyzed using LC-MS-MS. Concentrations ranged from 12.6 to 1,377 ng/mL. Additional analysis was performed to characterize the metabolic profile of N-ethyl pentylone using human liver microsomes (HLM), followed by confirmation of the presence of the proposed metabolites in a subset of the blood specimens and oral fluid specimens. Metabolomic analysis was performed using a liquid chromatograph quadrupole time-of-flight mass spectrometer (LC-QTOF), followed by data processing using MetabolitePilot™ software. In vivo verification of in vitro HLM-generated metabolites resulted in the confirmation of four metabolites. Reduction of the beta-ketone to an alcohol resulted in the most prominent metabolite found in the authentic specimens, and its uniqueness to N-ethyl pentylone leads to this metabolite being an appropriate biomarker to determine N-ethyl pentylone ingestion. This is the first study to report N-ethyl pentylone concentrations and to characterize the metabolic profile of N-ethyl pentylone.</description><subject>Adult</subject><subject>Benzodioxoles - blood</subject><subject>Benzodioxoles - poisoning</subject><subject>Biotransformation</subject><subject>Butylamines - blood</subject><subject>Butylamines - poisoning</subject><subject>Cause of Death</subject><subject>Chromatography, Liquid - methods</subject><subject>Drug Overdose - blood</subject><subject>Drug Overdose - diagnosis</subject><subject>Female</subject><subject>Forensic Toxicology - methods</subject><subject>Humans</subject><subject>Male</subject><subject>Metabolomics - methods</subject><subject>Microsomes, Liver - metabolism</subject><subject>Middle Aged</subject><subject>Psychotropic Drugs - blood</subject><subject>Psychotropic Drugs - poisoning</subject><subject>Reproducibility of Results</subject><subject>Saliva - metabolism</subject><subject>Substance Abuse Detection - methods</subject><subject>Tandem Mass Spectrometry</subject><subject>Young Adult</subject><issn>0146-4760</issn><issn>1945-2403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNo9kMlOwzAURS0EoqWw4QOQl4AUaseJ47ArVaGVGAWsI9uxqUtiR4mDyDfw06QDrN503l0cAE4xusIoJeMV92Px2aEw3gNDnEZxEEaI7IMhwhENooSiAThqmhVCmDJKDsEgTClmKEmG4OcxmPllV8BnZX1XOKvg-axabroLuLDefRvJvXG2uYYvLbfe-H78UnDqrDZ1ublBbnP4oDwXrjBewUXepxm9-4TGwknrl-udhPO25BbeGFe4jx4o4GulpCmVbY7BgeZFo052dQTeb2dv03lw_3S3mE7uA0lC4gMt0iQmiiWxlEIRLHMRES0JpQJrzkTCMGKcSJaGoUAJCVVKNUN5joSINc3JCFxuc2XtmqZWOqtqU_K6yzDK1kaz3mi2NdrDZ1u4akWp8n_0TyH5BT0_dkk</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Krotulski, Alex J</creator><creator>Papsun, Donna M</creator><creator>De Martinis, Bruno S</creator><creator>Mohr, Amanda L A</creator><creator>Logan, Barry K</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-1775-1882</orcidid></search><sort><creationdate>20180901</creationdate><title>N-Ethyl Pentylone (Ephylone) Intoxications: Quantitative Confirmation and Metabolite Identification in Authentic Human Biological Specimens</title><author>Krotulski, Alex J ; Papsun, Donna M ; De Martinis, Bruno S ; Mohr, Amanda L A ; Logan, Barry K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c323t-fb9753e875ccbe31cdb43fc366b1fa8b78108a3c8922b0732e96f80dd0bb5f6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Benzodioxoles - blood</topic><topic>Benzodioxoles - poisoning</topic><topic>Biotransformation</topic><topic>Butylamines - blood</topic><topic>Butylamines - poisoning</topic><topic>Cause of Death</topic><topic>Chromatography, Liquid - methods</topic><topic>Drug Overdose - blood</topic><topic>Drug Overdose - diagnosis</topic><topic>Female</topic><topic>Forensic Toxicology - methods</topic><topic>Humans</topic><topic>Male</topic><topic>Metabolomics - methods</topic><topic>Microsomes, Liver - metabolism</topic><topic>Middle Aged</topic><topic>Psychotropic Drugs - blood</topic><topic>Psychotropic Drugs - poisoning</topic><topic>Reproducibility of Results</topic><topic>Saliva - metabolism</topic><topic>Substance Abuse Detection - methods</topic><topic>Tandem Mass Spectrometry</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krotulski, Alex J</creatorcontrib><creatorcontrib>Papsun, Donna M</creatorcontrib><creatorcontrib>De Martinis, Bruno S</creatorcontrib><creatorcontrib>Mohr, Amanda L A</creatorcontrib><creatorcontrib>Logan, Barry K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of analytical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krotulski, Alex J</au><au>Papsun, Donna M</au><au>De Martinis, Bruno S</au><au>Mohr, Amanda L A</au><au>Logan, Barry K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>N-Ethyl Pentylone (Ephylone) Intoxications: Quantitative Confirmation and Metabolite Identification in Authentic Human Biological Specimens</atitle><jtitle>Journal of analytical toxicology</jtitle><addtitle>J Anal Toxicol</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>42</volume><issue>7</issue><spage>467</spage><epage>475</epage><pages>467-475</pages><issn>0146-4760</issn><eissn>1945-2403</eissn><abstract>N-ethyl pentylone (ephylone) has been identified as the most recent novel stimulant to emerge into the arena of evolving novel psychoactive substances (NPS). Due to its novelty, information regarding case reports with associated quantitative confirmations, biotransformation pathways, and identified unique metabolites will assist the scientific community in understanding the implications of the emergence and risks associated with N-ethyl pentylone use. Authentic blood specimens (n = 26) submitted as part of toxicological death investigations or drugged driving casework tested positive for N-ethyl pentylone, and were quantitatively analyzed by liquid chromatography tandem mass spectrometry (LC-MS-MS). N-ethyl pentylone concentrations ranged from 12 to 1,200 ng/mL, with mean (±standard deviation) and median concentrations of 313 (±366) and 125 ng/mL, respectively, excluding one case measured at 50,000 ng/mL. N-ethyl pentylone was often found in combination with other drugs of abuse and NPS, include a variety of novel opioids including fentanyl analogs. Oral fluid specimens (n = 5), collected from recreational drug users at a dance music festival, were quantitatively analyzed using LC-MS-MS. Concentrations ranged from 12.6 to 1,377 ng/mL. Additional analysis was performed to characterize the metabolic profile of N-ethyl pentylone using human liver microsomes (HLM), followed by confirmation of the presence of the proposed metabolites in a subset of the blood specimens and oral fluid specimens. Metabolomic analysis was performed using a liquid chromatograph quadrupole time-of-flight mass spectrometer (LC-QTOF), followed by data processing using MetabolitePilot™ software. In vivo verification of in vitro HLM-generated metabolites resulted in the confirmation of four metabolites. Reduction of the beta-ketone to an alcohol resulted in the most prominent metabolite found in the authentic specimens, and its uniqueness to N-ethyl pentylone leads to this metabolite being an appropriate biomarker to determine N-ethyl pentylone ingestion. This is the first study to report N-ethyl pentylone concentrations and to characterize the metabolic profile of N-ethyl pentylone.</abstract><cop>England</cop><pmid>29618077</pmid><doi>10.1093/jat/bky025</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-1775-1882</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adult Benzodioxoles - blood Benzodioxoles - poisoning Biotransformation Butylamines - blood Butylamines - poisoning Cause of Death Chromatography, Liquid - methods Drug Overdose - blood Drug Overdose - diagnosis Female Forensic Toxicology - methods Humans Male Metabolomics - methods Microsomes, Liver - metabolism Middle Aged Psychotropic Drugs - blood Psychotropic Drugs - poisoning Reproducibility of Results Saliva - metabolism Substance Abuse Detection - methods Tandem Mass Spectrometry Young Adult |
title | N-Ethyl Pentylone (Ephylone) Intoxications: Quantitative Confirmation and Metabolite Identification in Authentic Human Biological Specimens |
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