Investigation of a recently detected THCCOOH isomer: Post mortem findings and comparison with Δ8-THCCOOH. (December 2015)

• Record Type: Journal Article
• Authors: Hanisch, Stephanie; Paulke, Alexander; Toennes, Stefan W.
• Is Part Of: Forensic science international. Volume 257(2015)
• Page Start: 252
• Page End: 256
• Publication Date: 2015-12
• Subjects: Cannabinoids -- THCCOOH isomer -- Drug testing -- In-vitro metabolism -- CYP2C9; Medical jurisprudence -- Periodicals; Chemistry, Forensic -- Periodicals; Forensic Medicine -- Periodicals; Médecine légale -- Périodiques; Chimie légale -- Périodiques; Gerechtelijke geneeskunde; Gerechtelijke chemie; Gerechtelijke psychiatrie; Chemistry, Forensic; Medical jurisprudence; Electronic journals; Periodicals; Electronic journals; 614.1
• DOI: 10.1016/j.forsciint.2015.09.001
• Languages: English
• ISSNs: 0379-0738

Abstract

Highlights: Investigations on the nature of a previously unknown isomer of Δ 9 -THCCOOH. The Δ 8 -structure (e.g. Δ 8 -THCCOOH an isomer of Δ 9 -THCCOOH) is proposed. The isomer is not of Δ 8 -structure, nor formed CYP2C9-dependent. The isomer is also present in body fluids and post mortem tissues except for brain. The distribution of the isomer is similar to Δ 9 -THCCOOH in human body. Abstract: Background: An isomer of the non-psychoactive cannabinoid Δ 9 -THCCOOH was recently detected in blood from cannabis users. The structure of this compound is currently unknown. Therefore, further investigations were performed to elucidate its nature. Methods: Further biological specimens were analyzed using the previously published LC–MS/MS method to evaluate the distribution of this compound in the human body. Hypothetically, the unknown compound was isomeric in the position of the double bond, i.e. Δ 8 -THCCOOH. An in-vitro metabolism study on Δ 8 -THC and Δ 9 -THC was performed to compare the resulting metabolites with the unknown compound. Results: The unknown THCCOOH isomer was detected in all analyzed human body compartments (urine, bile, liver, lung and kidney) except for brain indicating that its detectability is not limited to blood. The in-vitro metabolism assay with the human CYP2C9 isoform led to the formation of THCOH and THCCOOH of Δ 8 -THC and Δ 9 -THC. However, the unknown isomer present in blood exhibited a different retention time than each of the metabolites formed. Conclusion: The unknown THCCOOH isomer accompanied THCCOOH and was detected in various human body compartments. The present in-vitro metabolism study proved that it is not of Δ 8 -THCCOOH structure nor that it is metabolically formed by the human CYP2C9 isoform.