A unique approach for in-situ monitoring of the THCA decarboxylation reaction in solid state

Olga Gigopulu; Nikola Geskovski; Gjoshe Stefkov; Veronika Stoilkovska Gjorgievska; Irena Slaveska Spirevska; Christian W Huck; Petre Makreski

doi:10.1016/j.saa.2021.120471

A unique approach for in-situ monitoring of the THCA decarboxylation reaction in solid state

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Feb 15;267(Pt 2):120471. doi: 10.1016/j.saa.2021.120471. Epub 2021 Oct 9.

Authors

Olga Gigopulu¹, Nikola Geskovski², Gjoshe Stefkov³, Veronika Stoilkovska Gjorgievska³, Irena Slaveska Spirevska⁴, Christian W Huck⁵, Petre Makreski⁶

Affiliations

¹ Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, Institute of Applied Chemistry and Pharmaceutical Analysis, Majka Tereza 47, 1000 Skopje, North Macedonia.
² Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, Institute of Pharmaceutical Technology, Majka Tereza 47, 1000 Skopje, North Macedonia. Electronic address: ngeskovski@ff.ukim.edu.mk.
³ Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, Institute of Pharmacognosy, Majka Tereza 47, 1000 Skopje, North Macedonia.
⁴ ReplekFarm, Kozle 188, 1000 Skopje, North Macedonia.
⁵ Institute of Analytical Chemistry and Radiochemistry, CCB - Center for Chemistry and Biomedicine, Leopold-Franzens University, Innrain 80-82, 6020 Innsbruck, Austria.
⁶ Ss. Cyril and Methodius University in Skopje, Faculty of Natural Sciences and Mathematics, Institute of Chemistry, Arhimedova 5, 1000 Skopje, North Macedonia. Electronic address: petremak@pmf.ukim.mk.

PMID: 34655978
DOI: 10.1016/j.saa.2021.120471

Abstract

The decarboxylation of Δ9-tetrahydrocannabinolic acid (THCA) plays pivotal role in the potency of medical cannabis and its extracts. Our present work aims to draw attention to mid-infrared (MIR) spectroscopy to in-situ monitor and decipher the THCA decarboxylation reaction in the solid state. The initial TG/DTG curves of THCA, for a first time, outlined the solid-solid decarboxylation dynamics, defined the endpoint of the process and the temperature of the maximal conversion rate, which aided in the design of the further IR experiment. Temperature controlled IR spectroscopy experiments were performed on both THCA standard and cannabis flower by providing detailed band assignment and conducting spectra-structure correlations, based on the concept of functional groups vibrations. Moreover, a multivariate statistical analysis was employed to address the spectral regions of utmost importance for the THCA → THC interconversion process. The principal component analysis model was reduced to two PCs, where PC1 explained 94.76% and 98.21% of the total spectral variations in the THCA standard and in the plant sample, respectively. The PC1 plot score of the THCA standard, as a function of the temperature, neatly complemented to the TG/DTG curves and enabled determination of rate constants for the decarboxylation reaction undertaken on several selected temperatures. The predictive capability of MIR was further demonstrated with PLS (R2X = 0.99, R2Y = 0.994 and Q2 = 0.992) using thermally treated flower samples that covered broad range of THCA/THC content. Consequently, a progress in elucidation of kinetic models of THCA decarboxylation in terms of fitting the experimental data for both, solid state standard substance and a plant flower, was achieved. The results open the horizon to promote an appropriate process analytical technology (PAT) in the outgrowing medical cannabis industry.

Keywords: Cannabinoids; HPLC; Infrared spectroscopy; Marijuana; Plant material; TG/DTG; Δ9-tetrahydrocannabinol (THC).

MeSH terms

Cannabis*
Decarboxylation
Dronabinol*
Flowers

Substances

Dronabinol