Isolation and Characterization of Impurities in Commercially Marketed Δ⁸-THC Products

Qualitative analysis of several commercial products containing Δ⁸-tetrahydrocannabinol (Δ⁸-THC) as a major component using GC-MS resulted in the identification of several impurities along with Δ⁸-THC. In an attempt to isolate and identify these impurities, a commercial Δ⁸-THC distillate was selected for the isolation work. Eleven impurities were isolated using a variety of chromatographic techniques, and their chemical structures were determined. These include Δ^4,8-iso-tetrahydrocannabinol (1), Δ⁴-iso-tetrahydrocannabinol (2), Δ⁸-cis-iso-tetrahydrocannabinol (3), 4,8-epoxy-iso-tetrahydrocannabinol (4), 8-hydroxy-iso-tetrahydrocannabinol (5), 9β-hydroxyhexahydrocannabinol (6), 9α-hydroxyhexa-hydrocannabinol (7), iso-tetrahydrocannabifuran (8), cannabicitran (CBT, 9), olivetol (10), and Δ⁹-THC (11). The chemical structures of the purified compounds were determined using several spectroscopic methods, including 1D (¹H, ¹³C, and DEPT-135) and 2D (COSY, HMQC, HMBC, and NOESY) NMR, LC-MS, and GC-MS. Other naturally occurring cannabinoids and impurities were also identified in GC-MS chromatograms but were not isolated. These were cannabidiol (CBD, 12), cannabinol (CBN, 13), hexahydrocannabinol (HHC, 14), and Δ⁸-tetrahydrocannabivarin (Δ⁸-THCV, 15). The chemical structure of Δ⁸-THCV (15), for which a standard was not available, was confirmed by partial synthesis and NMR analysis. This is the first report for many of the above compounds as well as Δ⁸-THCV as impurities in Δ⁸-THC products.