Thermal decarboxylation of acidic cannabinoids in Cannabis species: identification of transformed cannabinoids by UHPLC-Q/TOF–MS

Abstract

Decarboxylation of cannabidiolic acid (CBDA) is an important step for efficient production of the active pharmaceutical component cannabidiol (CBD) in Cannabis species. Acidic cannabinoids (ACBs) can be easily transformed into neutral cannabinoids via loss of carbon dioxide when exposed to heat. During the thermal process, several transformed products including psychotropic △9-tetrahydrocannabinol (△9-THC) and its isomers were produced through decarboxylation, hydration, isomerization, and oxidation, as identified by ultra-high-performance liquid chromatography quadrupole/time-of-flight mass spectrometry (UHPLC-Q/TOF MS). Their identification was carried out using authenticated standards and interpreting the MS/MS fragmentations. To investigate thermal decarboxylation, CBDA was extracted and isolated from inflorescence of Cannabis by ultrasonication extraction and two-step column chromatography. To investigate the decarboxylation yield of isolated CBDA and ACBs in Cannabis extract, samples were examined over a range of reaction temperatures (110–130 °C) and times (5–60 min). Time profiles of CBDA degradation and CBD formation were obtained as functions of the reaction temperature. In particular, most of the CBDA was converted into CBD at 130 °C for 20 min; this CBD was partially transformed to psychotropic THC isomers via cyclization. In addition to THC isomers, cannabielsoin acid (CBEA) and cannabielsoin (CBE) were also observed as minor oxidative transformed products. Based on structural identification and profiling data, thermal transformation pathways of CBDA are plausibly suggested. The results of decarboxylation of ACBs will provide important information on production of neutral cannabinoids, especially CBD, in Cannabis plants and quality control of Cannabis-based products in pharmaceutical and cosmetic industries.