Metabolism of novel opioid agonists U-47700 and U-49900 using human liver microsomes with confirmation in authentic urine specimens from drug users.
Identifieur interne : 000933 ( Main/Corpus ); précédent : 000932; suivant : 000934Metabolism of novel opioid agonists U-47700 and U-49900 using human liver microsomes with confirmation in authentic urine specimens from drug users.
Auteurs : Alex J. Krotulski ; Amanda L A. Mohr ; Donna M. Papsun ; Barry K. LoganSource :
- Drug testing and analysis [ 1942-7611 ] ; 2018.
English descriptors
- KwdEn :
- Adolescent (MeSH), Adult (MeSH), Analgesics, Opioid (chemistry), Analgesics, Opioid (metabolism), Analgesics, Opioid (urine), Benzamides (chemistry), Benzamides (metabolism), Benzamides (urine), Drug Users (MeSH), Humans (MeSH), Illicit Drugs (chemistry), Illicit Drugs (metabolism), Illicit Drugs (urine), Male (MeSH), Metabolome (physiology), Microsomes, Liver (metabolism), Young Adult (MeSH).
- MESH :
- chemical , chemistry : Analgesics, Opioid, Benzamides, Illicit Drugs.
- chemical , metabolism : Analgesics, Opioid, Benzamides, Illicit Drugs.
- chemical , urine : Analgesics, Opioid, Benzamides, Illicit Drugs.
- metabolism : Microsomes, Liver.
- physiology : Metabolome.
- Adolescent, Adult, Drug Users, Humans, Male, Young Adult.
Abstract
Recently, the number of adverse events, including death, involving novel opioids has continued to increase, providing additional and sustained challenges for forensic and medical communities. Identification of emerging novel opioids can be challenging, compounded by detection windows and unknown metabolic profiles. In this study, human liver microsomes were used for the generation of in vitro metabolic profiles of U-47700 and U-49900. Generated metabolites were analyzed via a SCIEX TripleTOF® 5600+ quadrupole time-of-flight mass spectrometer and resulting data files were processing using MetabolitePilot™. Characterized metabolites were verified in vivo by analysis of authentic human urine specimens collected after analytically confirmed cases of overdose involving U-47700 or U-49900. In total, four metabolites were identified and present in urine specimens for U-47700, and five metabolites for U-49900. N-Desmethyl-U-47700 was determined to be the primary metabolite of U-47700. Parent U-47700 was identified in all urine specimens. N-Desmethyl-U-47700 and N,N-didesmethyl-U-47700 were structurally confirmed for the first time during this study following acquisition of standard reference material. N-Desethyl-U-49900 was determined to be the primary metabolite of U-49900 following microsomal incubations, while N,N-didesethyl-N-desmethyl-U-49900 was the most abundant in a urine specimen. Similarities in metabolic transformation were identified between U-47700 and U-49900, resulting in a common metabolite and isomeric species. These phenomena should be considered in cases involving U-47700 or U-49900. This study is the first to map the metabolic profiles of U-47700 and U-49900 using human liver microsomes, as well as the first to report any literature involving U-49900 and analysis of case specimens.
DOI: 10.1002/dta.2228
PubMed: 28608586
Links to Exploration step
pubmed:28608586Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Metabolism of novel opioid agonists U-47700 and U-49900 using human liver microsomes with confirmation in authentic urine specimens from drug users.</title><author><name sortKey="Krotulski, Alex J" sort="Krotulski, Alex J" uniqKey="Krotulski A" first="Alex J" last="Krotulski">Alex J. Krotulski</name><affiliation><nlm:affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mohr, Amanda L A" sort="Mohr, Amanda L A" uniqKey="Mohr A" first="Amanda L A" last="Mohr">Amanda L A. Mohr</name><affiliation><nlm:affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Papsun, Donna M" sort="Papsun, Donna M" uniqKey="Papsun D" first="Donna M" last="Papsun">Donna M. Papsun</name><affiliation><nlm:affiliation>NMS Labs, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Logan, Barry K" sort="Logan, Barry K" uniqKey="Logan B" first="Barry K" last="Logan">Barry K. Logan</name><affiliation><nlm:affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>NMS Labs, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:28608586</idno><idno type="pmid">28608586</idno><idno type="doi">10.1002/dta.2228</idno><idno type="wicri:Area/Main/Corpus">000933</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000933</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Metabolism of novel opioid agonists U-47700 and U-49900 using human liver microsomes with confirmation in authentic urine specimens from drug users.</title><author><name sortKey="Krotulski, Alex J" sort="Krotulski, Alex J" uniqKey="Krotulski A" first="Alex J" last="Krotulski">Alex J. Krotulski</name><affiliation><nlm:affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mohr, Amanda L A" sort="Mohr, Amanda L A" uniqKey="Mohr A" first="Amanda L A" last="Mohr">Amanda L A. Mohr</name><affiliation><nlm:affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Papsun, Donna M" sort="Papsun, Donna M" uniqKey="Papsun D" first="Donna M" last="Papsun">Donna M. Papsun</name><affiliation><nlm:affiliation>NMS Labs, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Logan, Barry K" sort="Logan, Barry K" uniqKey="Logan B" first="Barry K" last="Logan">Barry K. Logan</name><affiliation><nlm:affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>NMS Labs, Willow Grove, Pennsylvania, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Drug testing and analysis</title><idno type="eISSN">1942-7611</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent (MeSH)</term><term>Adult (MeSH)</term><term>Analgesics, Opioid (chemistry)</term><term>Analgesics, Opioid (metabolism)</term><term>Analgesics, Opioid (urine)</term><term>Benzamides (chemistry)</term><term>Benzamides (metabolism)</term><term>Benzamides (urine)</term><term>Drug Users (MeSH)</term><term>Humans (MeSH)</term><term>Illicit Drugs (chemistry)</term><term>Illicit Drugs (metabolism)</term><term>Illicit Drugs (urine)</term><term>Male (MeSH)</term><term>Metabolome (physiology)</term><term>Microsomes, Liver (metabolism)</term><term>Young Adult (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Analgesics, Opioid</term><term>Benzamides</term><term>Illicit Drugs</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Analgesics, Opioid</term><term>Benzamides</term><term>Illicit Drugs</term></keywords><keywords scheme="MESH" type="chemical" qualifier="urine" xml:lang="en"><term>Analgesics, Opioid</term><term>Benzamides</term><term>Illicit Drugs</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Microsomes, Liver</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Metabolome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Drug Users</term><term>Humans</term><term>Male</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Recently, the number of adverse events, including death, involving novel opioids has continued to increase, providing additional and sustained challenges for forensic and medical communities. Identification of emerging novel opioids can be challenging, compounded by detection windows and unknown metabolic profiles. In this study, human liver microsomes were used for the generation of in vitro metabolic profiles of U-47700 and U-49900. Generated metabolites were analyzed via a SCIEX TripleTOF® 5600+ quadrupole time-of-flight mass spectrometer and resulting data files were processing using MetabolitePilot™. Characterized metabolites were verified in vivo by analysis of authentic human urine specimens collected after analytically confirmed cases of overdose involving U-47700 or U-49900. In total, four metabolites were identified and present in urine specimens for U-47700, and five metabolites for U-49900. N-Desmethyl-U-47700 was determined to be the primary metabolite of U-47700. Parent U-47700 was identified in all urine specimens. N-Desmethyl-U-47700 and N,N-didesmethyl-U-47700 were structurally confirmed for the first time during this study following acquisition of standard reference material. N-Desethyl-U-49900 was determined to be the primary metabolite of U-49900 following microsomal incubations, while N,N-didesethyl-N-desmethyl-U-49900 was the most abundant in a urine specimen. Similarities in metabolic transformation were identified between U-47700 and U-49900, resulting in a common metabolite and isomeric species. These phenomena should be considered in cases involving U-47700 or U-49900. This study is the first to map the metabolic profiles of U-47700 and U-49900 using human liver microsomes, as well as the first to report any literature involving U-49900 and analysis of case specimens.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28608586</PMID><DateCompleted><Year>2018</Year><Month>12</Month><Day>11</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1942-7611</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>1</Issue><PubDate><Year>2018</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Drug testing and analysis</Title><ISOAbbreviation>Drug Test Anal</ISOAbbreviation></Journal><ArticleTitle>Metabolism of novel opioid agonists U-47700 and U-49900 using human liver microsomes with confirmation in authentic urine specimens from drug users.</ArticleTitle><Pagination><MedlinePgn>127-136</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1002/dta.2228</ELocationID><Abstract><AbstractText>Recently, the number of adverse events, including death, involving novel opioids has continued to increase, providing additional and sustained challenges for forensic and medical communities. Identification of emerging novel opioids can be challenging, compounded by detection windows and unknown metabolic profiles. In this study, human liver microsomes were used for the generation of in vitro metabolic profiles of U-47700 and U-49900. Generated metabolites were analyzed via a SCIEX TripleTOF® 5600+ quadrupole time-of-flight mass spectrometer and resulting data files were processing using MetabolitePilot™. Characterized metabolites were verified in vivo by analysis of authentic human urine specimens collected after analytically confirmed cases of overdose involving U-47700 or U-49900. In total, four metabolites were identified and present in urine specimens for U-47700, and five metabolites for U-49900. N-Desmethyl-U-47700 was determined to be the primary metabolite of U-47700. Parent U-47700 was identified in all urine specimens. N-Desmethyl-U-47700 and N,N-didesmethyl-U-47700 were structurally confirmed for the first time during this study following acquisition of standard reference material. N-Desethyl-U-49900 was determined to be the primary metabolite of U-49900 following microsomal incubations, while N,N-didesethyl-N-desmethyl-U-49900 was the most abundant in a urine specimen. Similarities in metabolic transformation were identified between U-47700 and U-49900, resulting in a common metabolite and isomeric species. These phenomena should be considered in cases involving U-47700 or U-49900. This study is the first to map the metabolic profiles of U-47700 and U-49900 using human liver microsomes, as well as the first to report any literature involving U-49900 and analysis of case specimens.</AbstractText><CopyrightInformation>Copyright © 2017 John Wiley & Sons, Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Krotulski</LastName><ForeName>Alex J</ForeName><Initials>AJ</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-1775-1882</Identifier><AffiliationInfo><Affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mohr</LastName><ForeName>Amanda L A</ForeName><Initials>ALA</Initials><AffiliationInfo><Affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Papsun</LastName><ForeName>Donna M</ForeName><Initials>DM</Initials><AffiliationInfo><Affiliation>NMS Labs, Willow Grove, Pennsylvania, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Logan</LastName><ForeName>Barry K</ForeName><Initials>BK</Initials><AffiliationInfo><Affiliation>Center for Forensic Science Research and Education at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>NMS Labs, Willow Grove, Pennsylvania, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>07</Month><Day>26</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Drug Test Anal</MedlineTA><NlmUniqueID>101483449</NlmUniqueID><ISSNLinking>1942-7603</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000701">Analgesics, Opioid</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001549">Benzamides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013287">Illicit Drugs</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000614521">U-47700</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000628469">U-49900</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000701" MajorTopicYN="N">Analgesics, Opioid</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000652" MajorTopicYN="Y">urine</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001549" MajorTopicYN="N">Benzamides</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000652" MajorTopicYN="Y">urine</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055030" MajorTopicYN="Y">Drug Users</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013287" MajorTopicYN="N">Illicit Drugs</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName><QualifierName UI="Q000652" MajorTopicYN="Y">urine</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055442" MajorTopicYN="N">Metabolome</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008862" MajorTopicYN="N">Microsomes, Liver</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">U-47700</Keyword><Keyword MajorTopicYN="N">U-49900</Keyword><Keyword MajorTopicYN="N">authentic human urine specimen</Keyword><Keyword MajorTopicYN="N">high resolution mass spectrometry</Keyword><Keyword MajorTopicYN="N">human liver microsomes</Keyword><Keyword MajorTopicYN="N">novel opioids</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>04</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2017</Year><Month>06</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>06</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>6</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>12</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>6</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28608586</ArticleId><ArticleId IdType="doi">10.1002/dta.2228</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour 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