Real-time monitoring of CBDA decarboxylation in solid state and cannabis flowers using mid infrared spectroscopy coupled with multivariate analysis

Cannabidiolic acid (CBDA) is found in cannabis as genuine phytocompound of the well-known non-psychoactive cannabinoid - cannabidiol (CBD), notable for its various therapeutic purposes. Decarboxylation of CBDA to CBD is commonly used in the production of finished cannabis products, thus increasing its bioavailability, and making it more effective for various therapeutic purposes. Optimization of decarboxylation time and the possibility of monitoring this process in real-time is quite a challenge for the cannabis producers' R&D divisions, since incomplete decarboxylation is associated with quality and efficiency concerns, whereas prolonged reaction time can lead to potentially lower production efficacy. The purpose of this study is to emphasize the use of mid-infrared (MIR) spectroscopy for in-situ real-time monitoring and understanding of the CBDA decarboxylation process. For the first time, the TG/DTG curves of CBDA provided insights into the solid-solid decarboxylation dynamics, process endpoint, and maximal conversion rate temperature, which were used for designing the subsequent infrared experiments. In addition, the DSC curve illustrated the melting point of the pure CBDA. Temperature-controlled infrared spectroscopy studies were performed on CBDA standard and cannabis flowers followed by precise band assignment and spectra-structure correlations based on the idea of functional group vibrations. In order to investigate the spectral regions of major relevance for the CBDA to CBD interconversion process, a principal component analysis (PCA) was used. In the obtained models, PC1 was capable to describe 81.3 %, 77.8 % and 77 % of the total spectral fluctuations in the CBDA standard and two plant samples, respectively. The PC1 score plot of the CBDA standard (as a function of temperature) showed a perfect complementarity to the TG/DTG curve, indicating that PC1 of the MIR spectrum model may quantitatively describe the CBDA decarboxylation dynamics, which allowed for the derivation of decarboxylation rate constants for the CBDA standard and the plant material at prechosen temperatures. The temperature-controlled experiments revealed significantly higher kinetics constants of CBDA decarboxylation in the plant material compared to the CBDA standard and supported the assumption that the complex matrix in cannabis plants accelerates the conversion of CBDA to CBD. In this way, progress in the development and optimization of an efficient and fast approach for monitoring and elucidation of the phytocannabinoid decarboxylation process was made, launching the possibility for further employment in the medical cannabis industry.