Isomerization of delta‐9‐THC to delta‐8‐THC when tested as trifluoroacetyl‐, pentafluoropropionyl‐, or heptafluorobutyryl‐ derivatives

Abstract

For GC-MS analysis of delta-9-tetrahydrocannabinol (delta-9-THC), perfluoroacid anhydrides in combination with perfluoroalcohols are commonly used for derivatization. This reagent mixture is preferred because it allows simultaneous derivatization of delta-9-THC and its acid metabolite, 11-nor-delta-9-THC-9-carboxylic acid present in biological samples. When delta-9-THC was derivatized by trifluoroacetic anhydride/hexafluoroisopropanol (TFAA/HFIPOH) and analyzed by GC-MS using full scan mode (50-550 amu), two peaks (P1 and P2) with an identical molecular mass of 410 amu were observed. On the basis of the total ion chromatogram (TIC), P1 with a shorter retention time (RT) was the major peak (TIC 84%). To identify the peaks, delta-8-THC was also tested under the same conditions. The RT and spectra of the major peak (TIC 95%) were identical with that of P1 for delta-9-THC. A minor peak (5%) present also correlated well with the latter peak (P2) for the delta-9-THC derivative. The fragmentation pathway of P1 was primarily demethylation followed by retro Diels-Alder fragmentation (M - 15-68, base peak 100%) indicating P1 as a delta-8-THC-trifluoroacetyl compound. This indicated that delta-9-THC isomerized to delta-8-THC during derivatization with TFAA/HFIPOH. Similar results were also observed when delta-9-THC was derivatized with pentafluoropropionic anhydride/pentafluoropropanol or heptafluorobutyric anhydride/heptafluorobutanol. No isomerization was observed when chloroform was used in derivatization with TFAA. In this reaction, the peaks of delta-8-THC-TFA and delta-9-THC-TFA had retention times and mass spectra matching with P1 and P2, respectively. Because of isomerization, perfluoroacid anhydrides/perfluoroalcohols are not suitable derivatizing agents for analysis of delta-9-THC; whereas the TFAA in chloroform is suitable for the analysis.

Aerosol Gas-Phase Components from Cannabis E-Cigarettes and Dabbing: Mechanistic Insight and Quantitative Risk Analysis

“…Cannabinoids such as THC contain a terpene backbone, and it is not surprising that similar volatile products are generated from dabbing THC, SND, and terpenes alone . A diversity of degradation mechanisms may occur upon thermal treatment of THC, but the significant levels of isoprene seen when dabbing THC alone indicate that the isoprene formed undergoes oxidation to release methacrolein and methyl vinyl ketone, a mechanism for which has been described in the context of atmospheric oxidation. , Isoprene has been previously described as a neutral product formed during fragmentation of THC in electron impact mass spectrometry. − The nearly fivefold increase in isoprene released from THC amended with ∼10% terpenes compared to THC alone (Table ) suggests that terpenes release isoprene more readily than THC. Indeed, all identified VOCs form in higher amounts per milligram of product consumed when dabbing SND than from THC alone.…”

Cannabis Vaping: Existing and Emerging Modalities, Chemistry, and Pulmonary Toxicology

“…CBD conversion to tetrahydrocannabinols by acid catalysis (Figure ) was reported in the literature as early as 1940 by Adams et al, and at least one patent has been issued for this process . The ring-closing reaction to Δ 9 -THC is accompanied by the double-bond isomerization to Δ 8 -THC, which also occurs under acid catalysis, and generation of the latter may be favored by longer reaction times. The use of CBD as a substrate for the synthesis of other cannabinoids has been recently reviewed, and additional products that may result from these processes have been described. , Crude online guides exist for this synthesis, and it has been suggested that some Δ 8 -THC CEC manufacturers do not include a postreaction purification step, potentially resulting in traces of sulfuric acid, hydrochloric acid, trifluoroacetic acid, or p -toluenesulfonic acid .…”

Forensic Science

“…Cannabinoids. It has been shown that DELTA 9 -THC (9-THC) isomerized to DELTA 8 -THC (8-THC) during derivatization (374). Liquid-liquid or solid-liquid extraction was used to analyze for 9-THC commercial hemp products (375).…”