LC-MS/MS analysis of 11-nor-9-carboxy-hexahydrocannabinol (HHC-COOH) and 11-hydroxy-hexahydrocannabinol (HHC-OH) for verification of hexahydrocannabinol (HHC) intake

Natural and semi-synthetic cannabinoid analogs are getting increasing media attention for their recreative use as an alternative to traditional cannabis, in Sweden as well as internationally. To investigate an increasing number of urine samples incoming to our clinical laboratory that were screening...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Scandinavian journal of clinical and laboratory investigation Ročník 84; číslo 2; s. 109 - 114
Hlavní autoři: Pettersson-Pablo, Paul, Oxelbark, Joakim
Médium: Journal Article
Jazyk:angličtina
Vydáno: England 01.04.2024
Témata:
ISSN:0036-5513, 1502-7686, 1502-7686
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Abstract Natural and semi-synthetic cannabinoid analogs are getting increasing media attention for their recreative use as an alternative to traditional cannabis, in Sweden as well as internationally. To investigate an increasing number of urine samples incoming to our clinical laboratory that were screening positive, using a CEDIA THC-COOH immunoassay from ThermoFisher Scientific, but then testing negative using GC-MS based verification analysis, we developed an LC-MS/MS-method for verification of hexahydrocannabinol (HHC) and Δ8-tetrahydrocannabinol. Assessment of HHC intake was based on identification of the following four metabolites: 11-nor-9(R)-carboxy-hexahydrocannabinol (R-HHC-COOH), 11-nor-9(S)-carboxy-hexahydrocannabinol (S-HHC-COOH), 11-hydroxy-9(R)-hexahydrocannabinol (R-HHC-OH) and 11-hydroxy-9(S)-hexahydrocannabinol (S-HHC-OH). Out of 46 urine samples analysed in this study, 44 showed presence of HHC-metabolites, which indicate HHC as the main explanation for an increased number of negative verifications for THC-COOH. In these samples, the HHC-OH metabolites occurred at a higher concentration than R-HHC-COOH while S-HHC-COOH was only detected in few samples at low concentrations. R-HHC-COOH and S-HHC-COOH can easily be added to a pre-existing verification method for THC-COOH, and still show acceptable results, while HHC-OH requires an enzyme capable of hydrolysing the ether glucuronide bond.
AbstractList Natural and semi-synthetic cannabinoid analogs are getting increasing media attention for their recreative use as an alternative to traditional cannabis, in Sweden as well as internationally. To investigate an increasing number of urine samples incoming to our clinical laboratory that were screening positive, using a CEDIA THC-COOH immunoassay from ThermoFisher Scientific, but then testing negative using GC-MS based verification analysis, we developed an LC-MS/MS-method for verification of hexahydrocannabinol (HHC) and Δ8-tetrahydrocannabinol. Assessment of HHC intake was based on identification of the following four metabolites: 11-nor-9(R)-carboxy-hexahydrocannabinol (R-HHC-COOH), 11-nor-9(S)-carboxy-hexahydrocannabinol (S-HHC-COOH), 11-hydroxy-9(R)-hexahydrocannabinol (R-HHC-OH) and 11-hydroxy-9(S)-hexahydrocannabinol (S-HHC-OH). Out of 46 urine samples analysed in this study, 44 showed presence of HHC-metabolites, which indicate HHC as the main explanation for an increased number of negative verifications for THC-COOH. In these samples, the HHC-OH metabolites occurred at a higher concentration than R-HHC-COOH while S-HHC-COOH was only detected in few samples at low concentrations. R-HHC-COOH and S-HHC-COOH can easily be added to a pre-existing verification method for THC-COOH, and still show acceptable results, while HHC-OH requires an enzyme capable of hydrolysing the ether glucuronide bond.
Natural and semi-synthetic cannabinoid analogs are getting increasing media attention for their recreative use as an alternative to traditional cannabis, in Sweden as well as internationally. To investigate an increasing number of urine samples incoming to our clinical laboratory that were screening positive, using a CEDIA THC-COOH immunoassay from ThermoFisher Scientific, but then testing negative using GC-MS based verification analysis, we developed an LC-MS/MS-method for verification of hexahydrocannabinol (HHC) and Δ8-tetrahydrocannabinol. Assessment of HHC intake was based on identification of the following four metabolites: 11-nor-9(R)-carboxy-hexahydrocannabinol (R-HHC-COOH), 11-nor-9(S)-carboxy-hexahydrocannabinol (S-HHC-COOH), 11-hydroxy-9(R)-hexahydrocannabinol (R-HHC-OH) and 11-hydroxy-9(S)-hexahydrocannabinol (S-HHC-OH). Out of 46 urine samples analysed in this study, 44 showed presence of HHC-metabolites, which indicate HHC as the main explanation for an increased number of negative verifications for THC-COOH. In these samples, the HHC-OH metabolites occurred at a higher concentration than R-HHC-COOH while S-HHC-COOH was only detected in few samples at low concentrations. R-HHC-COOH and S-HHC-COOH can easily be added to a pre-existing verification method for THC-COOH, and still show acceptable results, while HHC-OH requires an enzyme capable of hydrolysing the ether glucuronide bond.Natural and semi-synthetic cannabinoid analogs are getting increasing media attention for their recreative use as an alternative to traditional cannabis, in Sweden as well as internationally. To investigate an increasing number of urine samples incoming to our clinical laboratory that were screening positive, using a CEDIA THC-COOH immunoassay from ThermoFisher Scientific, but then testing negative using GC-MS based verification analysis, we developed an LC-MS/MS-method for verification of hexahydrocannabinol (HHC) and Δ8-tetrahydrocannabinol. Assessment of HHC intake was based on identification of the following four metabolites: 11-nor-9(R)-carboxy-hexahydrocannabinol (R-HHC-COOH), 11-nor-9(S)-carboxy-hexahydrocannabinol (S-HHC-COOH), 11-hydroxy-9(R)-hexahydrocannabinol (R-HHC-OH) and 11-hydroxy-9(S)-hexahydrocannabinol (S-HHC-OH). Out of 46 urine samples analysed in this study, 44 showed presence of HHC-metabolites, which indicate HHC as the main explanation for an increased number of negative verifications for THC-COOH. In these samples, the HHC-OH metabolites occurred at a higher concentration than R-HHC-COOH while S-HHC-COOH was only detected in few samples at low concentrations. R-HHC-COOH and S-HHC-COOH can easily be added to a pre-existing verification method for THC-COOH, and still show acceptable results, while HHC-OH requires an enzyme capable of hydrolysing the ether glucuronide bond.
Author Pettersson-Pablo, Paul
Oxelbark, Joakim
Author_xml – sequence: 1
  givenname: Paul
  orcidid: 0000-0001-8458-6448
  surname: Pettersson-Pablo
  fullname: Pettersson-Pablo, Paul
  organization: Department of Laboratory Medicine, Clinical Chemistry, Örebro University Hospital, Örebro, Sweden, School of Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
– sequence: 2
  givenname: Joakim
  orcidid: 0000-0002-8101-5137
  surname: Oxelbark
  fullname: Oxelbark, Joakim
  organization: Department of Laboratory Medicine, Clinical Chemistry, Örebro University Hospital, Örebro, Sweden, School of Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
BackLink https://www.ncbi.nlm.nih.gov/pubmed/38529884$$D View this record in MEDLINE/PubMed
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-112636$$DView record from Swedish Publication Index (Örebro universitet)
BookMark eNp9kc9uEzEQhy1URNPCI4D22B6c-s_ascWp2gJBSpVDgas16_VSw8YO9i40D8R7stskHJDoYTQa6ftmpPmdoZMQg0PoNSVzShS5IoRLISifM8LKOeOcE8afoRkVhOGFVPIEzSYGT9ApOsv5GxlnrsoX6JQrwbRS5Qz9XlX49u7q9q6AAN0u-1zEtqAUh5iwxhZSHR92-N49wP2uSdFCCFD7ELviYrmscLVeLy9Ht5mcR-IpemLbmIqfLvnWW-h9DNO9_wmXhQ89fHcv0fMWuuxeHfo5-vz-3adqiVfrDx-r6xW2XJc9ZlwtBHOW1lpD6Zi2lqlW8LYuqWxK7RonnGpqKoAJrhoqqRRUWtDjo1oC_Bzh_d78y22H2myT30DamQje3Pgv1yamr2MNhlImuRz5iz2_TfHH4HJvNj5b13UQXByy4aTUC8aJ0iP65oAO9cY1f1cfoxiBt3vApphzcq2xvn_8UJ_Ad4YSMwVvjsGbKXhzCH60xT_28cDT3h-DCK6z
CitedBy_id crossref_primary_10_1002_dta_3871
crossref_primary_10_1093_jat_bkae091
crossref_primary_10_1016_j_cca_2025_120480
Cites_doi 10.1002/dta.1998
10.1093/jat/20.5.291
10.1002/dta.3519
10.3390/ph17020249
10.1002/dta.3190
10.1016/j.psc.2023.03.008
10.1002/dta.2230
10.1016/j.drugpo.2019.03.006
10.1093/jat/bkad059
10.1177/14690667231200139
10.1093/jat/bku075
10.2165/00003088-200342040-00003
10.1093/jat/19.5.292
ContentType Journal Article
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
7X8
AABEP
ADTPV
AOWAS
D8T
D91
ZZAVC
DOI 10.1080/00365513.2024.2333023
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
SWEPUB Örebro universitet full text
SwePub
SwePub Articles
SWEPUB Freely available online
SWEPUB Örebro universitet
SwePub Articles full text
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList
MEDLINE
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: 7X8
  name: MEDLINE - Academic
  url: https://search.proquest.com/medline
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Medicine
EISSN 1502-7686
EndPage 114
ExternalDocumentID oai_DiVA_org_oru_112636
38529884
10_1080_00365513_2024_2333023
Genre Journal Article
GroupedDBID ---
-~X
.55
.GJ
00X
03L
0R~
123
34G
36B
39C
3O-
4.4
53G
5RE
5VS
AAGDL
AAJKZ
AALIY
AALUX
AAMIU
AAORF
AAPUL
AAPXX
AAQQT
AAQRR
AAWTL
AAYXX
ABBKH
ABDBF
ABEIZ
ABJNI
ABLIJ
ABLJU
ABLKL
ABOCM
ABUPF
ABWCV
ABWVI
ABXYU
ABZEW
ACENM
ACGEJ
ACGFS
ACIEZ
ACKZS
ACOPL
ACUHS
ACYZI
ADCVX
ADFOM
ADFZZ
ADRBQ
ADXPE
AECIN
AEIIZ
AENEX
AEOZL
AFFNX
AFKVX
AFLEI
AFRVT
AGDLA
AGFJD
AGRBW
AGYJP
AIJEM
AIRBT
AJVHN
AJWEG
AKBVH
ALMA_UNASSIGNED_HOLDINGS
ALQZU
ALYBC
AMDAE
AWYRJ
BABNJ
BLEHA
BOHLJ
BRMBE
CAG
CCCUG
CITATION
COF
CS3
CYYVM
CZDIS
DKSSO
DRXRE
DU5
DWTOO
EAP
EAS
EBB
EBC
EBD
EBS
EBX
EHN
EJD
EMB
EMK
EMOBN
EPL
EPT
ESX
F5P
H13
HZ~
JENTW
KRBQP
KSSTO
KWAYT
KYCEM
L7B
LJTGL
M44
M4Z
NUSFT
O9-
OVD
P2P
QQXMO
Q~Q
RNANH
RVRKI
SV3
TASJS
TBQAZ
TDBHL
TEORI
TERGH
TFDNU
TFL
TFW
TUROJ
TUS
UEQFS
UHWXJ
V1S
WH7
X7M
ZGI
ZXP
~1N
ADYSH
CGR
CUY
CVF
ECM
EIF
NPM
7X8
AABEP
ADTPV
AOWAS
AQTUD
D8T
D91
ZZAVC
ID FETCH-LOGICAL-c394t-238752ec1b99a4e29cc28f53fb416d49ede5e8db15a2538d1616516ca9036f0a3
ISICitedReferencesCount 5
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001191006300001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 0036-5513
1502-7686
IngestDate Tue Nov 04 17:23:50 EST 2025
Thu Oct 02 12:29:31 EDT 2025
Thu Apr 03 07:06:55 EDT 2025
Sat Nov 29 02:41:45 EST 2025
Tue Nov 18 19:36:57 EST 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 2
Keywords Cannabis
narcotics
urine
cannabinoids
liquid Chromatography-Mass spectrometry
hydrolysis
immunoassay
Language English
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c394t-238752ec1b99a4e29cc28f53fb416d49ede5e8db15a2538d1616516ca9036f0a3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ORCID 0000-0002-8101-5137
0000-0001-8458-6448
OpenAccessLink https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-112636
PMID 38529884
PQID 3049723089
PQPubID 23479
PageCount 6
ParticipantIDs swepub_primary_oai_DiVA_org_oru_112636
proquest_miscellaneous_3049723089
pubmed_primary_38529884
crossref_citationtrail_10_1080_00365513_2024_2333023
crossref_primary_10_1080_00365513_2024_2333023
PublicationCentury 2000
PublicationDate 2024-04-01
PublicationDateYYYYMMDD 2024-04-01
PublicationDate_xml – month: 04
  year: 2024
  text: 2024-04-01
  day: 01
PublicationDecade 2020
PublicationPlace England
PublicationPlace_xml – name: England
PublicationTitle Scandinavian journal of clinical and laboratory investigation
PublicationTitleAlternate Scand J Clin Lab Invest
PublicationYear 2024
References e_1_3_2_9_1
e_1_3_2_17_1
e_1_3_2_8_1
e_1_3_2_18_1
e_1_3_2_7_1
e_1_3_2_19_1
e_1_3_2_2_1
e_1_3_2_20_1
e_1_3_2_10_1
e_1_3_2_11_1
e_1_3_2_6_1
e_1_3_2_12_1
e_1_3_2_5_1
e_1_3_2_13_1
e_1_3_2_4_1
e_1_3_2_15_1
Helander A (e_1_3_2_3_1) 2021; 118
Albertson TE (e_1_3_2_14_1) 2016; 441
Ferretti ML (e_1_3_2_16_1)
References_xml – ident: e_1_3_2_8_1
– ident: e_1_3_2_19_1
  doi: 10.1002/dta.1998
– ident: e_1_3_2_11_1
  doi: 10.1093/jat/20.5.291
– ident: e_1_3_2_5_1
  doi: 10.1002/dta.3519
– ident: e_1_3_2_10_1
  doi: 10.3390/ph17020249
– ident: e_1_3_2_12_1
  doi: 10.1002/dta.3190
– ident: e_1_3_2_2_1
  doi: 10.1016/j.psc.2023.03.008
– ident: e_1_3_2_20_1
  doi: 10.1002/dta.2230
– ident: e_1_3_2_6_1
– ident: e_1_3_2_15_1
  doi: 10.1016/j.drugpo.2019.03.006
– ident: e_1_3_2_16_1
  article-title: A survey study of individuals using hexahydrocannabinol cannabis products: use patterns and perceived effects
  publication-title: Cannabis Cannabinoid Res
– ident: e_1_3_2_17_1
  doi: 10.1093/jat/bkad059
– ident: e_1_3_2_9_1
  doi: 10.1177/14690667231200139
– ident: e_1_3_2_7_1
  doi: 10.1093/jat/bku075
– ident: e_1_3_2_13_1
– ident: e_1_3_2_4_1
  doi: 10.2165/00003088-200342040-00003
– ident: e_1_3_2_18_1
  doi: 10.1093/jat/19.5.292
– volume: 441
  start-page: 18
  year: 2016
  ident: e_1_3_2_14_1
  article-title: The changing drug culture: emerging drugs of abuse and legal highs
  publication-title: FP Essent
– volume: 118
  start-page: 21056
  year: 2021
  ident: e_1_3_2_3_1
  article-title: [Drug use and drug trends in Sweden 2010-2020 - results from urine drug testing in the workplace]
  publication-title: Lakartidningen
SSID ssj0003384
Score 2.391516
Snippet Natural and semi-synthetic cannabinoid analogs are getting increasing media attention for their recreative use as an alternative to traditional cannabis, in...
SourceID swepub
proquest
pubmed
crossref
SourceType Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage 109
SubjectTerms cannabinoids
Cannabis
Dronabinol - analogs & derivatives
Dronabinol - urine
Gas Chromatography-Mass Spectrometry - methods
Humans
hydrolysis
immunoassay
Liquid Chromatography-Mass Spectrometry
narcotics
Substance Abuse Detection - methods
Tandem Mass Spectrometry - methods
urine
Title LC-MS/MS analysis of 11-nor-9-carboxy-hexahydrocannabinol (HHC-COOH) and 11-hydroxy-hexahydrocannabinol (HHC-OH) for verification of hexahydrocannabinol (HHC) intake
URI https://www.ncbi.nlm.nih.gov/pubmed/38529884
https://www.proquest.com/docview/3049723089
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-112636
Volume 84
WOSCitedRecordID wos001191006300001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVAWR
  databaseName: Taylor & Francis Journals Complete
  customDbUrl:
  eissn: 1502-7686
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0003384
  issn: 0036-5513
  databaseCode: TFW
  dateStart: 19490101
  isFulltext: true
  titleUrlDefault: https://www.tandfonline.com
  providerName: Taylor & Francis
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1fb9MwELe6gaa9IP6vA6YgIcQeXBo7qe3HqTBVaF0rtUDfIsdxWEWXVF1bdR-IT8QX4pw4acroGA88NKoSn1359-v5Lr47I_TG82kYS8mw5jHFng8-K3ebIeah9IBAktEoSxQ-Y-fnfDQS_VrtZ5ELs5ywJOGrlZj-V6jhHoBtUmf_Ae6yU7gB3wF0uALscL0T8Gdt3B2AOHjoslJxxHVxks6wwErOwnR1jS_0Sl5cR7CAySSR4CCnE2Nudjpt3O71OuZ1gXmpDnJZq9sl8vYmZBHmy0QfVSzRbUJGYpzM5feNaKSByhJt5HJstwisuVymcJofZalr4gPG60Ih64iCfpakBBOd4L4M892lagxkb6UnoY0S_5SCEX1ZfftBqkEz2mpsUOngM7WqKj0_dc5Sl1T0s5vVYri5bhSBlrRlDrxpmJEahFJzolK1PSA9vcx4Q7lPBLfjbBbsLh7toHuE-cKo2uHp19I8oJR7RSqZKfL-pzH30V7Ry6a9dMMJ-q3CbWYVDR-iB9adcU5yGj5CNZ08RntdG7DxBP3I2Pi-O3AKLjpp7NyFi867gonHIBs5t_Mwb23aAgedKgfNeNsEjp2cf0_R59OPw3YH25NBsKLCm2OwM5lPtHJDIaSniVCK8NincQj-ReQJHWlf8yh0fUlgRY_ArWn5bktJAbMdNyV9hnaTNNEHyPG9SEmmGFjanicUC1XoutolRDFNYu3XkVfMf6Bs2XxzesskcNfVdTMEA4NgYBGso0YpNs3rxvxN4HUBbgAa3mzbyUSni6vAbIQzQptc1NHzHPWyy4IldfQ2p0H5xJSN_zD-chKks2_wWQQmV5C2Drd28QLtr_9gL9HufLbQr9B9tZyPr2ZHaIeN-FHG5F__s9Pr
linkProvider Taylor & Francis
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=LC-MS%2FMS+analysis+of+11-nor-9-carboxy-hexahydrocannabinol+%28HHC-COOH%29+and+11-hydroxy-hexahydrocannabinol+%28HHC-OH%29+for+verification+of+hexahydrocannabinol+%28HHC%29+intake&rft.jtitle=Scandinavian+journal+of+clinical+and+laboratory+investigation&rft.au=Pettersson-Pablo%2C+Paul&rft.au=Oxelbark%2C+Joakim&rft.date=2024-04-01&rft.eissn=1502-7686&rft.volume=84&rft.issue=2&rft.spage=109&rft_id=info:doi/10.1080%2F00365513.2024.2333023&rft_id=info%3Apmid%2F38529884&rft.externalDocID=38529884
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0036-5513&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0036-5513&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0036-5513&client=summon