First detection of ethylphenidate in human fatalities after ethylphenidate intake
Abstract Methylphenidate, a psychostimulant drug from the group of amphetamines is, among others, established in the treatment of attention deficit hyperactivity disorder and narcolepsy. It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate...
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description | Abstract Methylphenidate, a psychostimulant drug from the group of amphetamines is, among others, established in the treatment of attention deficit hyperactivity disorder and narcolepsy. It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate was detected in human plasma in small amounts. However, ethylphenidate is sold as “research chemical” via the Internet. It was put under German narcotics law in July 2013. In a recent case, where a deceased person was found in his apartment, the police seized a plastic bag with the inscription “ethylphenidate”. An autopsy of the 32-year-old man yielded a mitral valve endocarditis, which must have persisted a while before death, in combination with a pneumonia. At the Forensic Toxicological Centre (FTC) in Munich femoral blood, liver, pericardium fluid, urine, stomach content and hair of the deceased were analyzed for ethylphenidate after sample preparation by an LC-Triple TOF 5600. Calibration curves were spiked with a methanolic 1 mg/mL solution of ethylphenidate (substance provided by the State Office of Criminal Investigation in Munich) in whole blood in comparison to liver and femoral blood, in serum in comparison to pericardium fluid and in urine in comparison to urine and stomach content, respectively. Ethylphenidate was detected in all analyzed matrices. The spectrums of the human specimen were compared to those obtained from the calibration curves and identified as ethylphenidate. The measured concentrations were for femoral blood 110 ng/mL, for liver 180 ng/g, for pericardium fluid 131 ng/mL, for urine 987 ng/mL and for stomach content 20.7 ng/mL, respectively. The stomach contained 200 mL of a brownish-coloured liquid, resulting in a total amount of 4000 ng ethylphenidate. The lowest calibrator for whole blood and serum was 1 ng/mL and for urine 10 ng/mL. As far as it is known to the authors, these are the first ethylphenidate levels measured in a case of ethylphenidate intake. Therefore these results can only be compared to methylphenidate concentrations with therapeutic levels ranging from 5 to 60 ng/mL in serum. As the toxic levels for methylphenidate start from approximately 500 ng/mL serum, we estimate that ethylphenidate in the concentrations mentioned above is not in a directly lethal range. But it has to be considered, that amphetamine-like drugs as methylphenidate are known for their cardiovascular side effects (like tachycardia and arrhythmi |
doi_str_mv | 10.1016/j.forsciint.2014.07.017 |
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It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate was detected in human plasma in small amounts. However, ethylphenidate is sold as “research chemical” via the Internet. It was put under German narcotics law in July 2013. In a recent case, where a deceased person was found in his apartment, the police seized a plastic bag with the inscription “ethylphenidate”. An autopsy of the 32-year-old man yielded a mitral valve endocarditis, which must have persisted a while before death, in combination with a pneumonia. At the Forensic Toxicological Centre (FTC) in Munich femoral blood, liver, pericardium fluid, urine, stomach content and hair of the deceased were analyzed for ethylphenidate after sample preparation by an LC-Triple TOF 5600. Calibration curves were spiked with a methanolic 1 mg/mL solution of ethylphenidate (substance provided by the State Office of Criminal Investigation in Munich) in whole blood in comparison to liver and femoral blood, in serum in comparison to pericardium fluid and in urine in comparison to urine and stomach content, respectively. Ethylphenidate was detected in all analyzed matrices. The spectrums of the human specimen were compared to those obtained from the calibration curves and identified as ethylphenidate. The measured concentrations were for femoral blood 110 ng/mL, for liver 180 ng/g, for pericardium fluid 131 ng/mL, for urine 987 ng/mL and for stomach content 20.7 ng/mL, respectively. The stomach contained 200 mL of a brownish-coloured liquid, resulting in a total amount of 4000 ng ethylphenidate. The lowest calibrator for whole blood and serum was 1 ng/mL and for urine 10 ng/mL. As far as it is known to the authors, these are the first ethylphenidate levels measured in a case of ethylphenidate intake. Therefore these results can only be compared to methylphenidate concentrations with therapeutic levels ranging from 5 to 60 ng/mL in serum. As the toxic levels for methylphenidate start from approximately 500 ng/mL serum, we estimate that ethylphenidate in the concentrations mentioned above is not in a directly lethal range. But it has to be considered, that amphetamine-like drugs as methylphenidate are known for their cardiovascular side effects (like tachycardia and arrhythmia) and might therefore have contributed to death, which was attributed to endocarditis in combination with pneumonia.</description><identifier>ISSN: 0379-0738</identifier><identifier>EISSN: 1872-6283</identifier><identifier>DOI: 10.1016/j.forsciint.2014.07.017</identifier><identifier>PMID: 25161162</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Adult ; Amphetamines ; Attention deficit hyperactivity disorder ; Blood ; Calibration ; Central Nervous System Stimulants - analysis ; Dopamine ; Endocarditis - pathology ; Ethylphenidate ; Fluid dynamics ; Fluids ; Forensic sciences ; Gastrointestinal Contents - chemistry ; Hair - chemistry ; Humans ; Hydrochloric acid ; LC-Triple TOF ; Liver ; Liver - chemistry ; Male ; Medical treatment ; Methylphenidate ; Methylphenidate - analogs & derivatives ; Methylphenidate - analysis ; Pathology ; Pericardium ; Pericardium - chemistry ; Pneumonia - pathology ; Postmortem toxicology ; Ritalinic acid ; Serums ; Stomach ; Urine</subject><ispartof>Forensic science international, 2014-10, Vol.243, p.126-129</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2014 Elsevier Ireland Ltd</rights><rights>Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.</rights><rights>Copyright Elsevier Limited Oct 1, 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-4d548480dd491a9d817552860ab8b9b672415a679b5c0e10e86f0c38568b9f4f3</citedby><cites>FETCH-LOGICAL-c487t-4d548480dd491a9d817552860ab8b9b672415a679b5c0e10e86f0c38568b9f4f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1614105346?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25161162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krueger, J</creatorcontrib><creatorcontrib>Sachs, H</creatorcontrib><creatorcontrib>Musshoff, F</creatorcontrib><creatorcontrib>Dame, T</creatorcontrib><creatorcontrib>Schaeper, J</creatorcontrib><creatorcontrib>Schwerer, M</creatorcontrib><creatorcontrib>Graw, M</creatorcontrib><creatorcontrib>Roider, G</creatorcontrib><title>First detection of ethylphenidate in human fatalities after ethylphenidate intake</title><title>Forensic science international</title><addtitle>Forensic Sci Int</addtitle><description>Abstract Methylphenidate, a psychostimulant drug from the group of amphetamines is, among others, established in the treatment of attention deficit hyperactivity disorder and narcolepsy. It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate was detected in human plasma in small amounts. However, ethylphenidate is sold as “research chemical” via the Internet. It was put under German narcotics law in July 2013. In a recent case, where a deceased person was found in his apartment, the police seized a plastic bag with the inscription “ethylphenidate”. An autopsy of the 32-year-old man yielded a mitral valve endocarditis, which must have persisted a while before death, in combination with a pneumonia. At the Forensic Toxicological Centre (FTC) in Munich femoral blood, liver, pericardium fluid, urine, stomach content and hair of the deceased were analyzed for ethylphenidate after sample preparation by an LC-Triple TOF 5600. Calibration curves were spiked with a methanolic 1 mg/mL solution of ethylphenidate (substance provided by the State Office of Criminal Investigation in Munich) in whole blood in comparison to liver and femoral blood, in serum in comparison to pericardium fluid and in urine in comparison to urine and stomach content, respectively. Ethylphenidate was detected in all analyzed matrices. The spectrums of the human specimen were compared to those obtained from the calibration curves and identified as ethylphenidate. The measured concentrations were for femoral blood 110 ng/mL, for liver 180 ng/g, for pericardium fluid 131 ng/mL, for urine 987 ng/mL and for stomach content 20.7 ng/mL, respectively. The stomach contained 200 mL of a brownish-coloured liquid, resulting in a total amount of 4000 ng ethylphenidate. The lowest calibrator for whole blood and serum was 1 ng/mL and for urine 10 ng/mL. As far as it is known to the authors, these are the first ethylphenidate levels measured in a case of ethylphenidate intake. Therefore these results can only be compared to methylphenidate concentrations with therapeutic levels ranging from 5 to 60 ng/mL in serum. As the toxic levels for methylphenidate start from approximately 500 ng/mL serum, we estimate that ethylphenidate in the concentrations mentioned above is not in a directly lethal range. But it has to be considered, that amphetamine-like drugs as methylphenidate are known for their cardiovascular side effects (like tachycardia and arrhythmia) and might therefore have contributed to death, which was attributed to endocarditis in combination with pneumonia.</description><subject>Adult</subject><subject>Amphetamines</subject><subject>Attention deficit hyperactivity disorder</subject><subject>Blood</subject><subject>Calibration</subject><subject>Central Nervous System Stimulants - analysis</subject><subject>Dopamine</subject><subject>Endocarditis - pathology</subject><subject>Ethylphenidate</subject><subject>Fluid dynamics</subject><subject>Fluids</subject><subject>Forensic sciences</subject><subject>Gastrointestinal Contents - chemistry</subject><subject>Hair - chemistry</subject><subject>Humans</subject><subject>Hydrochloric acid</subject><subject>LC-Triple TOF</subject><subject>Liver</subject><subject>Liver - chemistry</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Methylphenidate</subject><subject>Methylphenidate - analogs & derivatives</subject><subject>Methylphenidate - analysis</subject><subject>Pathology</subject><subject>Pericardium</subject><subject>Pericardium - chemistry</subject><subject>Pneumonia - pathology</subject><subject>Postmortem toxicology</subject><subject>Ritalinic acid</subject><subject>Serums</subject><subject>Stomach</subject><subject>Urine</subject><issn>0379-0738</issn><issn>1872-6283</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNks1u1DAUhS0EotPCK0AkNmwSruPfbJCqilKkSggBa8txbjSeZpzBdpDm7XE0pUhl05UX_u6xzz2HkLcUGgpUftg14xyT8z7kpgXKG1ANUPWMbKhWbS1bzZ6TDTDV1aCYPiPnKe0AQIhWviRnraCSUtluyLdrH1OuBszosp9DNY8V5u1xOmwx-MFmrHyotsvehmq02U4-e0yVHTPG_8Fs7_AVeTHaKeHr-_OC_Lz-9OPqpr79-vnL1eVt7bhWueaD4JprGAbeUdsNmqryOS3B9rrveqlaToWVquuFA6SAWo7gmBayXI98ZBfk_Un3EOdfC6Zs9j45nCYbcF6SKfY6Jpjm3RNQ6MpaO7mi7x6hu3mJoRgpFOUUBOOyUOpEuTinFHE0h-j3Nh4NBbMGZHbmISCzBmRAmRJQmXxzr7_0exwe5v4mUoDLE4Bld789RlNUMDgcfCwRmWH2T3jk4yMNN_ngnZ3u8IjpnyOTWgPm-9qTtSaUAzAo3fkDhj-5jQ</recordid><startdate>20141001</startdate><enddate>20141001</enddate><creator>Krueger, J</creator><creator>Sachs, H</creator><creator>Musshoff, F</creator><creator>Dame, T</creator><creator>Schaeper, J</creator><creator>Schwerer, M</creator><creator>Graw, M</creator><creator>Roider, G</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><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><scope>7U5</scope><scope>8FD</scope><scope>L7M</scope></search><sort><creationdate>20141001</creationdate><title>First detection of ethylphenidate in human fatalities after ethylphenidate intake</title><author>Krueger, J ; Sachs, H ; Musshoff, F ; Dame, T ; Schaeper, J ; Schwerer, M ; Graw, M ; Roider, G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-4d548480dd491a9d817552860ab8b9b672415a679b5c0e10e86f0c38568b9f4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Amphetamines</topic><topic>Attention deficit hyperactivity disorder</topic><topic>Blood</topic><topic>Calibration</topic><topic>Central Nervous System Stimulants - analysis</topic><topic>Dopamine</topic><topic>Endocarditis - pathology</topic><topic>Ethylphenidate</topic><topic>Fluid dynamics</topic><topic>Fluids</topic><topic>Forensic sciences</topic><topic>Gastrointestinal Contents - chemistry</topic><topic>Hair - chemistry</topic><topic>Humans</topic><topic>Hydrochloric acid</topic><topic>LC-Triple TOF</topic><topic>Liver</topic><topic>Liver - chemistry</topic><topic>Male</topic><topic>Medical treatment</topic><topic>Methylphenidate</topic><topic>Methylphenidate - analogs & derivatives</topic><topic>Methylphenidate - analysis</topic><topic>Pathology</topic><topic>Pericardium</topic><topic>Pericardium - chemistry</topic><topic>Pneumonia - pathology</topic><topic>Postmortem toxicology</topic><topic>Ritalinic acid</topic><topic>Serums</topic><topic>Stomach</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krueger, J</creatorcontrib><creatorcontrib>Sachs, H</creatorcontrib><creatorcontrib>Musshoff, F</creatorcontrib><creatorcontrib>Dame, T</creatorcontrib><creatorcontrib>Schaeper, J</creatorcontrib><creatorcontrib>Schwerer, M</creatorcontrib><creatorcontrib>Graw, M</creatorcontrib><creatorcontrib>Roider, G</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><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><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Forensic science international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krueger, J</au><au>Sachs, H</au><au>Musshoff, F</au><au>Dame, T</au><au>Schaeper, J</au><au>Schwerer, M</au><au>Graw, M</au><au>Roider, G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>First detection of ethylphenidate in human fatalities after ethylphenidate intake</atitle><jtitle>Forensic science international</jtitle><addtitle>Forensic Sci Int</addtitle><date>2014-10-01</date><risdate>2014</risdate><volume>243</volume><spage>126</spage><epage>129</epage><pages>126-129</pages><issn>0379-0738</issn><eissn>1872-6283</eissn><abstract>Abstract Methylphenidate, a psychostimulant drug from the group of amphetamines is, among others, established in the treatment of attention deficit hyperactivity disorder and narcolepsy. It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate was detected in human plasma in small amounts. However, ethylphenidate is sold as “research chemical” via the Internet. It was put under German narcotics law in July 2013. In a recent case, where a deceased person was found in his apartment, the police seized a plastic bag with the inscription “ethylphenidate”. An autopsy of the 32-year-old man yielded a mitral valve endocarditis, which must have persisted a while before death, in combination with a pneumonia. At the Forensic Toxicological Centre (FTC) in Munich femoral blood, liver, pericardium fluid, urine, stomach content and hair of the deceased were analyzed for ethylphenidate after sample preparation by an LC-Triple TOF 5600. Calibration curves were spiked with a methanolic 1 mg/mL solution of ethylphenidate (substance provided by the State Office of Criminal Investigation in Munich) in whole blood in comparison to liver and femoral blood, in serum in comparison to pericardium fluid and in urine in comparison to urine and stomach content, respectively. Ethylphenidate was detected in all analyzed matrices. The spectrums of the human specimen were compared to those obtained from the calibration curves and identified as ethylphenidate. The measured concentrations were for femoral blood 110 ng/mL, for liver 180 ng/g, for pericardium fluid 131 ng/mL, for urine 987 ng/mL and for stomach content 20.7 ng/mL, respectively. The stomach contained 200 mL of a brownish-coloured liquid, resulting in a total amount of 4000 ng ethylphenidate. The lowest calibrator for whole blood and serum was 1 ng/mL and for urine 10 ng/mL. As far as it is known to the authors, these are the first ethylphenidate levels measured in a case of ethylphenidate intake. Therefore these results can only be compared to methylphenidate concentrations with therapeutic levels ranging from 5 to 60 ng/mL in serum. As the toxic levels for methylphenidate start from approximately 500 ng/mL serum, we estimate that ethylphenidate in the concentrations mentioned above is not in a directly lethal range. But it has to be considered, that amphetamine-like drugs as methylphenidate are known for their cardiovascular side effects (like tachycardia and arrhythmia) and might therefore have contributed to death, which was attributed to endocarditis in combination with pneumonia.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>25161162</pmid><doi>10.1016/j.forsciint.2014.07.017</doi><tpages>4</tpages></addata></record> |
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subjects | Adult Amphetamines Attention deficit hyperactivity disorder Blood Calibration Central Nervous System Stimulants - analysis Dopamine Endocarditis - pathology Ethylphenidate Fluid dynamics Fluids Forensic sciences Gastrointestinal Contents - chemistry Hair - chemistry Humans Hydrochloric acid LC-Triple TOF Liver Liver - chemistry Male Medical treatment Methylphenidate Methylphenidate - analogs & derivatives Methylphenidate - analysis Pathology Pericardium Pericardium - chemistry Pneumonia - pathology Postmortem toxicology Ritalinic acid Serums Stomach Urine |
title | First detection of ethylphenidate in human fatalities after ethylphenidate intake |
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