QC and product screening of medicinal cannabis with NIR spectroscopy

5 sept. 2022

Article

Close-up image of cannabis flower with trichomes.

Cannabis et spectroscopie proche infrarouge

La spectroscopie dans le proche infrarouge (NIRS) est une technique d'analyse rapide et peu coûteuse, utilisée pour effectuer le contrôle de la qualité (CQ) et le dépistage des produits sur divers produits du cannabis, y compris le chanvre. Elle peut déterminer le profil des cannabinoïdes ou même la puissance des fleurs de cannabis séchées. Le NIRS peut également être utilisé pour le CQ des huiles de cannabis, des cires, des teintures et d'autres formulations..

"Cannabis" est le terme général couvrant un groupe de trois plantes aux propriétés psychoactives variables : Cannabis sativa, Cannabis indica et Cannabis ruderalis [1]. La plante de cannabis est utilisée comme médicament, aliment et pour sa fibre depuis des milliers d'années. Les fleurs et certaines feuilles des plantes de cannabis sont recouvertes de minuscules structures cristallines appelées "trichomes", et ce sont ces structures qui sont responsables de la production des cannabinoïdes utilisés dans de nombreux autres produits.

Lorsque les fleurs de ces plantes sont récoltées et séchées, on obtient l'une des drogues les plus courantes au monde..

What are the most important and well-known cannabis compounds?

Cannabis contains more than 120 compounds known as «cannabinoids» [1]. Each cannabinoid’s effects are not yet completely known, but experts have a decent understanding of three of them: cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabinol (THC, or Delta-9-THC). Each of them has its own effects and uses [1]:

CBD. This is a psychoactive cannabinoid, yet it’s non-intoxicating and non-euphoric, meaning it won’t get you «high». It’s often used to help reduce inflammation and pain. Researchers are still trying to fully understand the effectiveness of CBD’s medical use.
CBG. This cannabinoid was first isolated in 1964. Research into CBG is still at preclinical stages, but available studies suggest that it holds considerable therapeutic promise. CBG's properties may surpass those of THC without the intoxicating effect. There is also evidence to suggest that CBG may offer anticancer, antidepressant, and antibacterial qualities.
THC. This is the main psychoactive compound in cannabis. THC is responsible for the «high» that most people associate with cannabis.

Legality of cannabis and hemp

Cannabis is illegal in many countries. However, more and more places are starting to legalize it for medical as well as recreational uses. Hemp, which typically has a low THC content, is still used in many places for its fiber to create products like textiles, rope, and even biodegradable plastics.

The laws regarding cannabis possession and use also vary for each country. Some consider any kind of cannabis possession a serious crime, others permit products containing only CBD, and very few allow people to use products with THC (whether for medical or recreational purposes).

What cannabis products are available on the market?

Legal cannabis can appear in a wide assortment of products other than the typical dried flower or wax that is smoked or otherwise ingested. Several options are available, depending on the country you live in and the legality of different cannabidiol compounds. The list below (not comprehensive) [2] shows how the market for cannabis products has evolved over the past decade as it becomes more accepted in various places.

This article is only meant for informational purposes. Metrohm does not endorse the use of these products in any way.

Cannabis oils
Cannabis beauty and skin care products
Cannabis edibles (e.g., beverages, chocolates, gummies, and other snacks)
Cannabis capsules
Cannabis dog treats

An employee drying harvested cannabis.

Drying, curing, and processing cannabis

Drying and curing are important for successfully processing cannabis plants after harvest to end products like cannabis oils, cannabis capsules, etc. The plant material must be dried immediately after harvest to avoid spoilage. Most of the moisture should be removed within the first three days, then slowed to avoid drying out over the next several days [3]. The curing process is an extension of drying, but in an altered environment to facilitate plant processes over a period of weeks. The dried cannabis is placed in airtight containers only opened periodically. This draws out moisture from within the flower buds while enhancing quality and potency [3]. After curing, the cannabis is ready to be processed into its end product.

One such product, CBD oil, is made by extraction from dried cannabis flower and then diluting it with a carrier oil (e.g., coconut or hemp seed oil, Figure 1). Two suitable options are available for the extraction process: ethanol extraction or supercritical CO₂ extraction.

To produce cannabis capsules or tablets, the dried cannabis needs to be heated for 10 minutes at 99–104°C. This will decarboxylate the raw plant material and render it more potent.

To screen these processes, Metrohm offers applicative solutions for ground plant materials as raw material testing and for oils. NIR spectroscopy is an analytical technique that is particularly suited for making quality control of these products more efficient and cost-effective.

In the remainder of this article, a short overview of NIRS is presented followed by an application example for the medicinal cannabis industry, concluding with how medicinal cannabis producers can benefit from NIRS in their QC process.

NIRS technology – a short overview

The interaction between light and matter is a well-known process. Light used in spectroscopic methods is typically not described by the applied energy, but in many cases by the wavelength or wavenumbers.

A NIR spectrometer (such as the Metrohm DS2500 Liquid Analyzer or the Metrohm DS2500 Solid Analyzer) measures this interaction to generate spectra such as those displayed in Figure 2. NIRS is especially sensitive to the presence of certain functional groups (e.g., -CH, -NH, -OH, and -SH). Therefore, NIR spectroscopy is an ideal method to quantify chemical parameters including the amount of THC, CBD, CBG, and water content (moisture) in cannabis and its end products.

All of this information is contained in a single NIR spectrum, making this method suitable for quick multiparameter analysis.

NIRS measuring modes

The measuring mode is dependent on the sample type. The transmission mode is generally an appropriate procedure for analyzing liquids like cannabis oils. For transmission (Figure 3b), the NIR light will travel through the sample while being absorbed. Any unabsorbed NIR light reflects to the detector.

The transflection mode is generally an appropriate procedure for analyzing creams. This mode is also used when only very small sample quantities of sample are available, as in the case of cannabis. For transflection (Figure 4b), the NIR light passes through the sample, then reflected by the diffuse reflector travels again through the sample while being absorbed. Unabsorbed NIR light is then detected at the end of the analysis.

The diffuse reflection mode is generally an appropriate procedure for analyzing solid samples like dried cannabis flower. For diffuse reflection (Figure 5b), the NIR light illuminates the sample and any unabsorbed NIR light reflects back to the detector.

The procedure to obtain NIR spectra as shown in Figure 2 already highlights two major advantages of NIR spectroscopy: simplicity regarding sample measurement and speed:

Fast technique with results in less than a minute.
Little to no sample preparation required.
Low cost per sample – no chemicals or solvents needed.
Environmentally friendly technique – no waste generated.
Non-destructive – precious samples can be reused after analysis.
Easy to operate – inexperienced users are immediately successful.

For more detailed information about NIRS as a secondary technique, please read our previous blog posts.

Benefits of NIRS: Part 1

Benefits of NIRS: Part 2

Benefits of NIRS: Part 3

Benefits of NIRS: Part 4

NIRS as an ASTM compliant tool for QC

ASTM E1655 (Standard Practices for Infrared Multivariate Quantitative Analysis) is a guide for the multivariate calibration of infrared spectrometers used for determining physical or chemical characteristics of materials. These practices are applicable to analyses conducted in the near-infrared (NIR) spectral region (roughly 780 to 2500 nm) through the mid-infrared (MIR) spectral region (roughly 4000 to 400 cm⁻¹).

Applications and parameters for QC of medicinal cannabis with NIRS

Medicinal cannabis products are subjected to standardized test methods to determine their chemical properties. Laboratory testing is an indispensable part of R&D and quality control. Table 1 outlines some of the most relevant test parameters for QC of medicinal cannabis.

Product	Parameters	Conventional method	Related NIRS applications
CBD oils	CBD content	HPLC	AN-NIR-088
Dried cannabis	THC, CBD, and CBG content	HPLC	AN-NIR-101

A turnkey solution for dried cannabis analysis

The Metrohm NIRS solution for medicinal cannabis analysis comes with ready to use pre-calibration models for the determination of THC, CBD, CBG, and even moisture content based on more than 700 real product spectra (Table 2). These pre-calibrations allow the Metrohm solution to be used as a validated calibration model without any method development.

Parameter	Range	SECV	R²
THC	0.3–19.3%	0.73 wt%	0.979
CBD	0.1–18.5%	0.75 wt%	0.978
CBG	0.1–3.0%	0.17 wt%	0.849
Moisture	5.4–7.5%	0.21 wt%	0.953

Figure 6 shows the results of an example of the determination of THC, CBD, and CBG content in medicinal cannabis. The corresponding correlation plots show that the models for these three parameters are robust. Furthermore, the Standard Error of Cross Validation (SECV) values are close to the Standard Error of Calibration (SEC) for each parameter measured.

Summary

NIR spectroscopy is excellently suited for the analysis of several key quality parameters in dried cannabis. Compared to the primary method (HPLC), the time to result is a major advantage of NIRS since a single measurement is performed within one minute versus approximately 30 minutes with HPLC. In addition, samples measured by NIRS are not destroyed, and chemical reagents are unnecessary – saving even more costs. Another positive aspect of using near-infrared spectroscopy as an alternative technology for QC of medicinal cannabis and its products is the ease of handling so that even shift workers can perform these analyses without issue. Furthermore, the Vision Air software from Metrohm is fully compliant with 21 CFR Part 11 and USP <856> guidelines.

References

What Is Cannabis? Facts About Its Components, Effects, and Hazards. Healthline. https://www.healthline.com/health/what-is-cannabis (accessed 2022-07-14).
Fiorillo, S. 7 Cannabis Products On the Rise. TheStreet. https://www.thestreet.com/lifestyle/5-cannabis-products-on-rise-14578907 (accessed 2022-07-14).
dhydratech. Cannabis Drying & Curing 101. Dhydra Technologies. https://dhydra.com/cannabis-drying/ (accessed 2022-07-14).