8β-OH-THC and 8β,11-diOH-THC—minor metabolites with major informative value?

Abstract

The ∆9-tetrahydrocannabinol (THC) metabolites 8β-hydroxy-THC and 8β,11-dihydroxy-THC are mentioned in the literature as potential blood markers of recent cannabis use. However, the formation of these metabolites in in vivo detectable concentrations has been described controversially. Therefore, the aim of this study was to verify the in vivo metabolism of 8β-hydroxy-THC and 8β,11-dihydroxy-THC in order to evaluate their potential as blood markers of recent cannabis use. First, we developed and validated a solid-phase-extraction method coupled with gas chromatography-mass spectrometry in order to enable the selective and very sensitive determination of 8β-hydroxy-THC and 8β,11-dihydroxy-THC. The application of this method in the analysis of 70 authentic plasma samples of cannabis users revealed positive results for both analytes. We detected 8β-hydroxy-THC in three and 8β,11-dihydroxy-THC in 37 out of the 70 analyzed samples. For 8β-hydroxy-THC, all of the three positive results were below the limit of quantification (LOQ; 0.3 ng/mL) but above the limit of detection (LOD; 0.2 ng/mL). For 8β,11-dihydroxy-THC, only two positive results were below the LOQ (0.4 ng/mL) but above the LOD (0.3 ng/mL); the remaining 35 were quantified. Hence, we were able to prove the in vivo metabolism from THC to both 8β-hydroxy-THC and 8β,11-dihydroxy-THC in detectable concentrations. The quantitative comparison of 8β-hydroxy-THC and 8β,11-dihydroxy-THC with the main cannabinoids THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC revealed no further informative value for 8β-hydroxy-THC regarding the last time of cannabis consumption. However, the detectability from 8β,11-dihydroxy-THC compared to 11-hydroxy-THC suggests a shorter detection time for 8β,11-dihydroxy-THC and thereby a promising application of this metabolite as a blood marker of recent cannabis use.

Investigation of phase II metabolism of 11-hydroxy-Δ-9-tetrahydrocannabinol and metabolite verification by chemical synthesis of 11-hydroxy-Δ-9-tetrahydrocannabinol-glucuronide

“…The metabolites O1-O3 are assumed to be OH-THC derivates, as the exact mass fits the OH-THC derivates and the HESI(+)-MS-2 spectra showed similar neutral losses as the known metabolites 11-OH-Δ-9-THC and 8-OH-Δ-9-THC. The biotransformation of different hydroxy-metabolites is in line with several studies of in vivo and/or in vitro hydroxylation of (−)-Δ-9-THC [4][5][6][23][24][25][26]. In the range of 2 to 4 min, the signals can be assigned to in source fragments of OH-THC-glucuronides because they have the same retention time as the m/z 507.2589 of the glucuronides.…”

Fiber spray ionization mass spectrometry in forensic chemistry: A screening of drugs of abuse and direct determination of cocaine in urine

“…However, the signal at m/z 381 attributed to the chlorine adduct of cannabigerolic acid (CBGA) or cannabitriol (CBT), or their isomers, 47,48 was detected with an intensity more than three times higher using PSI(−). In addition, 8β,11-diOH-Δ 9 -THC, a Cannabis metabolite used as a blood marker for drug consumption screening, 49 was identified with better sensitivity by PSI(−) than by FSI(−). Using NH 4 OH as the ionizing agent also did not cause any improvement in signal intensity from FSI(−) analysis, whereas for PSI(−) an increase of up to five times in the signal intensities was observed (Figure 3), which may be explained by the occurrence of strong interactions between the paper and analytes that make the desorption process on the paper surface difficult.…”

Toxicogenetic analysis of Δ9-THC-metabolizing enzymes

“…1): In phase I, the majority of Δ9-THC is hydroxylated to 11-OH-Δ9-THC via CYP2C9 and CYP2C19 [15]. An alternative minor route is Δ9-THC m e t a b o l i s m t o 8 β -O H -Δ 9 -T H C a n d 9 , 1 0epoxyhexahydrocannabinol via CYP3A4 [16,17]. 11-OH-Δ9-THC is further oxidized to the psychoinactive Δ9-THC-COOH.…”