Mid-infrared spectroscopy as process analytical technology tool for estimation of THC and CBD content in Cannabis flowers and extracts.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most notable Cannabis components with pharmacological activity and their content in the plant flowers and extracts are considered as critical quality parameters. The new Medical Cannabis industry needs to adopt the quality standards of the pharmaceutical industry, however, the variability of phytocannabinoids content in the plant material often exerts an issue in the inconsistency of the finished product quality parameters. Sampling problems and sample representativeness is a major limitation in the end-point testing, particularly when the expected variation of the product quality parameters is high. Therefore, there is an obvious need for the introduction of Process Analytical Technology (PAT) for continuous monitoring of the critical quality parameters throughout the production processes. Infrared spectroscopy is a promising analytical technique that is consistent with the PAT requirements and its implementation depends on the advances in instrumentation and chemometrics that will facilitate the qualitative and quantitative aspects of the technique. Our present work aims in highlighting the potential of mid-infrared (MIR) spectroscopy as PAT in the quantification of the main phytocannabinoids (THC and CBD), considered as critical qualitymaterial parameters in the production of Cannabis plant and extract. A detailed assignment of the bands related to the molecules of interest (THC, CBD) was performed, the spectral features of the decarboxylation of native flowers were identified, and the specified bands for the acid forms (THCA, CBDA) were assigned and thoroughly explained. Further, multivariate models were constructed for the prediction of both THC and CBD content in extract and flower samples from various origins, and their prediction ability was tested on a separate sample set. Savitskzy-Golay smoothing and the second derivative of the native MIR spectra (1800-400 cm