Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, Institute of Applied Chemistry and Pharmaceutical Analysis, Majka Tereza 47, 1000 Skopje, North Macedonia.
Ss. Cyril and Methodius University in Skopje, Faculty of Pharmacy, Institute of Pharmaceutical Technology, Majka Tereza 47, 1000 Skopje, North Macedonia.
Spectrochim Acta A Mol Biomol Spectrosc. 2022 Feb 15;267(Pt 2):120471. doi: 10.1016/j.saa.2021.120471. Epub 2021 Oct 9.
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.
Δ9-四氢大麻酸（THCA）的脱羧作用在医用大麻及其提取物的效力中起着关键作用。我们目前的工作旨在引起人们对中红外（MIR）光谱的关注，以原位监测和破译固态下的 THCA 脱羧反应。THCA 的初始 TG/DTG 曲线首次概述了固-固脱羧动力学，定义了过程的终点和最大转化率的温度，这有助于进一步设计 IR 实验。通过提供详细的波段分配并基于官能团振动的概念进行光谱-结构相关性研究，对 THCA 标准品和大麻花进行了温度控制的红外光谱实验。此外，还采用多元统计分析来解决对 THCA→THC 相互转化过程最重要的光谱区域。主成分分析模型减少到两个 PCs，其中 PC1 分别解释了 THCA 标准品和植物样品总光谱变化的 94.76%和 98.21%。THCA 标准品的 PC1 图谱得分随温度的变化，与 TG/DTG 曲线很好地互补，并能够确定在几个选定温度下进行的脱羧反应的速率常数。使用涵盖广泛 THCA/THC 含量范围的经热处理的花样品进一步证明了 MIR 的预测能力，PLS（R2X=0.99、R2Y=0.994 和 Q2=0.992）。因此，在为固态标准物质和植物花拟合实验数据方面，在阐明 THCA 脱羧动力学模型方面取得了进展。这些结果为日益发展的医用大麻产业中推广适当的过程分析技术（PAT）开辟了道路。
