Hexahydrocannabinol (HHC) is an emerging semi-synthetic cannabinoid, that is obtained from cyclization of cannabidiol and subsequent hydrogenation. As a potentially legal alternative of Δ9-tetrahydrocannabinol (Δ9-THC), it is increasingly seized in the United States and Europe. The aims of this study were to investigate the metabolism of HHC in pooled human liver S9 fraction (pHLS9), in rat, and human samples. Additionally, a locally obtained low-THC cannabis product was investigated that was advertised with elevated concentration of HHC. Overall, HHC formed an 11-HO metabolite, as well as a carboxy metabolite. While only the parent compound was detected in rat urine and feces, the hydroxy metabolite was additionally detected in pHLS9 and human plasma. The carboxy metabolite was only detectable in human plasma. The metabolism corresponded well to that of Δ9-THC, although glucuronidation and the formation of an 8-HO metabolite was not observed. Detectability of HHC and its carboxy metabolite in rat urine was investigated using GC-MS, but neither the parent compound, nor the metabolite were detectable. The investigated low-THC cannabis product appeared to be an actual cannabis product, since in addition to HHC, cannabinol, cannabidiol, and Δ9-THC were detected after qualitative analysis. Estimation of its content revealed 30.6 % HHC but also 4 % of Δ9-THC.

中文翻译：

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使用 HPLC-HRMS/MS 对人类样品、混合人类肝脏 S9 级分、大鼠样品和药品中的半合成大麻素六氢大麻酚进行分析毒理学研究。

六氢大麻酚（HHC）是一种新兴的半合成大麻素，由大麻二酚环化和随后的氢化获得。作为 Δ9-四氢大麻酚 (Δ9-THC) 的潜在合法替代品，它在美国和欧洲越来越多地被缉获。本研究的目的是研究大鼠和人类样本中混合的人肝脏 S9 组分 (pHLS9) 中 HHC 的代谢。此外，还对当地获得的低 THC 大麻产品进行了调查，该产品的广告中 HHC 浓度较高。总体而言，HHC 形成了 11-HO 代谢物以及羧基代谢物。虽然在大鼠尿液和粪便中仅检测到母体化合物，但在 pHLS9 和人血浆中还检测到羟基代谢物。羧基代谢物仅在人血浆中可检测到。尽管没有观察到葡萄糖醛酸化和 8-H2O 代谢物的形成，但其代谢与 Δ9-THC 的代谢一致。使用 GC-MS 研究了大鼠尿液中 HHC 及其羧基代谢物的可检测性，但母体化合物和代谢物均未检测到。所调查的低 THC 大麻产品似乎是真正的大麻产品，因为除了 HHC 之外，定性分析后还检测到大麻酚、大麻二酚和 Δ9-THC。对其含量的估计显示出 30.6% 的 HHC，以及 4% 的 Δ9-THC。