Raeber Justine, Bajor Bryan, Poetzsch Michael, Steuer Christian
Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Swiss Drug Testing GmbH, Winterthur, Switzerland.
Phytochem Anal. 2025 Jan;36(1):205-217. doi: 10.1002/pca.3432. Epub 2024 Aug 5.
Cannabis sativa L. is renowned for its medicinal and recreational uses. With the increasing global legalization of C. sativa L.-based products for medicinal purposes, there is a growing need for well-characterized products. While the stability of cannabinoids such as tetrahydrocannabinol and cannabidiol is well understood, information on the chemical and enantiomeric stability of terpenes remains scarce. This is despite the fact that terpenes are also thought to have pharmacological activity and may contribute to the overall effect of C. sativa L.
To address these challenges, four analytical methods based on chiral, polar, and apolar gas chromatographic separation combined with either MS or FID detection were developed and validated. These methods successfully separated and quantified a total of 29 terpenes, including 13 enantiomers and 5 diastereomers specific to C. sativa L. Furthermore, terpenes and authentic C. sativa L. flowers and extracts were subjected to UV and heat treatments to observe potential degradation reactions over time.
Each terpene generates a unique pattern of degradation products resulting in a diverse array of oxidation and cyclization products. P-cymene was identified as a major product of terpene aging. Notably, no enantiomeric conversion was detected, suggesting that the formation of (-)-α-pinene in cannabis extracts, for example, originates from other terpenes.
Terpenes have different degradation rates, even though they are structurally similar. In addition, cultivar- and growth-condition-specific enantiomeric ratios were observed in C. sativa L., confirming that enantiomer production is species-specific and has to be considered for therapeutical applications.
大麻因其药用和娱乐用途而闻名。随着全球范围内基于大麻的药用产品合法化程度的提高，对特征明确的产品的需求也日益增长。虽然诸如四氢大麻酚和大麻二酚等大麻素的稳定性已为人熟知，但关于萜类化合物的化学和对映体稳定性的信息仍然匮乏。尽管萜类化合物也被认为具有药理活性，并且可能对大麻的整体效果有贡献。
为应对这些挑战，开发并验证了四种基于手性、极性和非极性气相色谱分离并结合质谱或氢火焰离子化检测器检测的分析方法。这些方法成功分离并定量了总共29种萜类化合物，包括13种对映体和5种大麻特有的非对映体。此外，对萜类化合物以及纯正的大麻花和提取物进行紫外线和热处理，以观察随时间推移可能发生的降解反应。
每种萜类化合物都会产生独特的降解产物模式，从而产生各种各样的氧化和环化产物。对异丙基甲苯被确定为萜类化合物老化的主要产物。值得注意的是，未检测到对映体转化，这表明例如大麻提取物中（-）-α-蒎烯的形成源自其他萜类化合物。
萜类化合物尽管结构相似，但具有不同的降解速率。此外，在大麻中观察到了特定品种和生长条件下的对映体比例，这证实了对映体的产生具有物种特异性，在治疗应用中必须予以考虑。
