{"title":"Cross-reactivity of the epimers of 11-nor-9-carboxy-hexahydrocannabinol, metabolites of hexahydrocannabinol, with panel tests for urinary Δ<sup>9</sup>-tetrahydrocannabinol metabolites.","authors":"Kenji Tsujikawa, Yuki Okada, Hiroki Segawa, Tadashi Yamamuro, Kenji Kuwayama, Tatsuyuki Kanamori, Yuko T Iwata","doi":"10.1007/s11419-025-00717-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The epimers of 11-nor-9-carboxy-hexahydrocannabinol (HHC-COOH) have been identified as metabolites of hexahydrocannabinol (HHC) in human urine. Owing to the similarity of chemical structures to 11-nor-9-carboxy-Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC-COOH), a major urinary metabolite of Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC), HHC-COOH may show cross-reactivity in panel tests for urinary Δ<sup>9</sup>-THC metabolites. The authors have evaluated the cross-reactivity of HHC-COOH epimers in three commercial panel tests.</p><p><strong>Methods: </strong>Human urine spiked with 9α- and 9β-HHC-COOH (final concentrations: 20-500 ng/mL) was subjected to three panel tests (Driven Flow THC L50, IVeX-Screen THC L50-S, and AccuSign THC) with a nominal cutoff concentration of 50 ng/mL for Δ<sup>9</sup>-THC-COOH. Additionally, an intact urine sample from an alleged HHC user was used.</p><p><strong>Results: </strong>The lowest concentrations judged as positive were 100-500 ng/mL for 9α-HHC-COOH and 50-100 ng/mL for 9β-HHC-COOH. Intact urine samples from an alleged HHC user, whose 9α-/9β-HHC-COOH concentrations (ng/mL) were < 4.0/25.5 before alkaline hydrolysis and 13.4/132.2 after alkaline hydrolysis, were positive for all three panel tests.</p><p><strong>Conclusions: </strong>Both epimers of HHC-COOH showed cross-reactivity in three panel tests. The reactivity of 9β-HHC-COOH was found to be higher than that of 9α-HHC-COOH. The urine test results from the alleged HHC user suggested that the acyl glucuronides of HHC-COOH also exhibited cross-reactivity. Users of panel tests for urinary Δ<sup>9</sup>-THC metabolites should pay attention to false positives potentially caused by HHC metabolites.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Forensic Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11419-025-00717-4","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Cross-reactivity of the epimers of 11-nor-9-carboxy-hexahydrocannabinol, metabolites of hexahydrocannabinol, with panel tests for urinary Δ9-tetrahydrocannabinol metabolites.
Purpose: The epimers of 11-nor-9-carboxy-hexahydrocannabinol (HHC-COOH) have been identified as metabolites of hexahydrocannabinol (HHC) in human urine. Owing to the similarity of chemical structures to 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THC-COOH), a major urinary metabolite of Δ9-tetrahydrocannabinol (Δ9-THC), HHC-COOH may show cross-reactivity in panel tests for urinary Δ9-THC metabolites. The authors have evaluated the cross-reactivity of HHC-COOH epimers in three commercial panel tests.
Methods: Human urine spiked with 9α- and 9β-HHC-COOH (final concentrations: 20-500 ng/mL) was subjected to three panel tests (Driven Flow THC L50, IVeX-Screen THC L50-S, and AccuSign THC) with a nominal cutoff concentration of 50 ng/mL for Δ9-THC-COOH. Additionally, an intact urine sample from an alleged HHC user was used.
Results: The lowest concentrations judged as positive were 100-500 ng/mL for 9α-HHC-COOH and 50-100 ng/mL for 9β-HHC-COOH. Intact urine samples from an alleged HHC user, whose 9α-/9β-HHC-COOH concentrations (ng/mL) were < 4.0/25.5 before alkaline hydrolysis and 13.4/132.2 after alkaline hydrolysis, were positive for all three panel tests.
Conclusions: Both epimers of HHC-COOH showed cross-reactivity in three panel tests. The reactivity of 9β-HHC-COOH was found to be higher than that of 9α-HHC-COOH. The urine test results from the alleged HHC user suggested that the acyl glucuronides of HHC-COOH also exhibited cross-reactivity. Users of panel tests for urinary Δ9-THC metabolites should pay attention to false positives potentially caused by HHC metabolites.
期刊介绍：
The journal Forensic Toxicology provides an international forum for publication of studies on toxic substances, drugs of abuse, doping agents, chemical warfare agents, and their metabolisms and analyses, which are related to laws and ethics. It includes original articles, reviews, mini-reviews, short communications, and case reports. Although a major focus of the journal is on the development or improvement of analytical methods for the above-mentioned chemicals in human matrices, appropriate studies with animal experiments are also published.
Forensic Toxicology is the official publication of the Japanese Association of Forensic Toxicology (JAFT) and is the continuation of the Japanese Journal of Forensic Toxicology (ISSN 0915-9606).
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