Russo Fabiana, Tolomeo Francesco, Angela Vandelli Maria, Biagini Giuseppe, Laganà Aldo, Laura Capriotti Anna, Cerrato Andrea, Carbone Luigi, Perrone Elisabetta, Cavazzini Alberto, Maiorano Vincenzo, Gigli Giuseppe, Cannazza Giuseppe, Citti Cinzia
Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41125 - Modena, Italy; Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 - Modena, Italy.
Institute of Nanotechnology - CNR NANOTEC, Campus Ecotekne, Via Monteroni, 73100 - Lecce, Italy.
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Apr 15;1221:123682. doi: 10.1016/j.jchromb.2023.123682. Epub 2023 Mar 21.
The evaluation of the chiral composition of phytocannabinoids in the cannabis plant is particularly important as the pharmacological effects of the (+) and (-) enantiomers of these compounds are completely different. Chromatographic attempts to assess the presence of the minor (+) enantiomers of the main phytocannabinoids, cannabidiolic acid (CBDA) and trans-Δ-tetrahydrocannabinolic acid (trans-Δ-THCA), were carried out on heated plant extracts for the determination of the corresponding decarboxylated species, cannabidiol (CBD) and trans-Δ-tetrahydrocannabinol (trans-Δ-THC), respectively. This process produces an altered phytocannabinoid composition with several new and unknown decomposition products. The present work reports for the first time the stereoselective synthesis of the pure (+) enantiomers of the main phytocannabinoids, trans-CBDA, trans-Δ-THCA, trans-CBD and trans-Δ-THC, and the development and optimization of an achiral-chiral liquid chromatography method coupled to UV and high-resolution mass spectrometry detection in reversed phase conditions (RP-HPLC-UV-HRMS) for the isolation of the single compounds and evaluation of their actual enantiomeric composition in plant. The isolation of the peaks with the achiral stationary phase ensured the absence of interferences that could potentially co-elute with the analytes of interest in the chiral analysis. The method applied to the Italian medicinal cannabis variety FM2 revealed no trace of the (+) enantiomers for all phytocannabinoids under investigation before and after decarboxylation, thus suggesting that the extraction procedure does not lead to an inversion of configuration.
评估大麻植物中植物大麻素的手性组成尤为重要，因为这些化合物的（+）和（-）对映体的药理作用完全不同。为了分别测定相应的脱羧产物大麻二酚（CBD）和反式Δ-四氢大麻酚（反式Δ-THC），对加热后的植物提取物进行了色谱分析，以评估主要植物大麻素大麻二酚酸（CBDA）和反式Δ-四氢大麻酚酸（反式Δ-THCA）的次要（+）对映体的存在情况。这个过程会产生一种改变了的植物大麻素组成，伴有几种新的和未知的分解产物。本研究首次报道了主要植物大麻素反式CBDA、反式Δ-THCA、反式CBD和反式Δ-THC的纯（+）对映体的立体选择性合成，以及一种非手性-手性液相色谱方法的开发和优化，该方法与紫外和高分辨率质谱检测相结合，在反相条件下（RP-HPLC-UV-HRMS）用于分离单一化合物并评估其在植物中的实际对映体组成。使用非手性固定相分离峰确保了在手性分析中不会出现可能与目标分析物共洗脱的干扰物。应用于意大利药用大麻品种FM2的该方法显示，在脱羧前后，所有被研究的植物大麻素均未检测到（+）对映体的痕迹，因此表明提取过程不会导致构型翻转。
