The a dagger 9-tetrahydrocannabinol (THC) metabolites 8 beta-hydroxy-THC and 8 beta,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 8 beta-hydroxy-THC and 8 beta,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 8 beta-hydroxy-THC and 8 beta,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 8 beta-hydroxy-THC in three and 8 beta,11-dihydroxy-THC in 37 out of the 70 analyzed samples. For 8 beta-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 8 beta,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 8 beta-hydroxy-THC and 8 beta,11-dihydroxy-THC in detectable concentrations. The quantitative comparison of 8 beta-hydroxy-THC and 8 beta,11-dihydroxy-THC with the main cannabinoids THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC revealed no further informative value for 8 beta-hydroxy-THC regarding the last time of cannabis consumption. However, the detectability from 8 beta,11-dihydroxy-THC compared to 11-hydroxy-THC suggests a shorter detection time for 8 beta,11-dihydroxy-THC and thereby a promising application of this metabolite as a blood marker of recent cannabis use.
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