Opportunities for Mass Spectrometry in the Cannabis Industry
The legal cannabis industry in North America is worth over $10 billion and employs more than a quarter of a million people, and yet the industry as a whole is decidedly still in its infancy. By comparison, the most recent future projections (from April 2019) expect the global legal cannabis market to be worth over $146 billion USD by the year 2025.
Given the potential for such great value, it is important that the industry has the correct tools to deal with this sort of growth without falling victim to those who may skirt the standards of safety and integrity for personal gain. For this, the cannabis industry may wish to look to the more established pharmaceutical and food and beverage industries for good industry standard practice.
One of the routine analysis methods being used in these industries is mass spectrometry, an analytical technique which ionizes chemical species in order to create a spectrum based on their charge-to-mass ratio. A new review published in the Journal of The American Society for Mass Spectrometry has examined the current challenges facing the development of the cannabis industry, and seeks to identify opportunities for techniques involving mass spectrometry to demonstrate their merits when it comes to cannabis analysis and testing.
Application 1: Potency Testing
While industry regulations do vary considerably depending on which state or which country is being profiled, potency testing is almost universally a certain requirement in the regulated marketplace. It usually concerns the determination of the percentage of tetrahydrocannabinol (THC) and cannabidiol (CBD) in cannabis flowers, or in other cannabis products such as edibles.
According to the review, HPLC/PDA (high performance liquid chromatography using a photodiode array detector) is the currently the favored method for potency testing. The analytical procedure itself is fairly easy to perform and inexpensive to employ, which has helped to cement its place in the industry.
However, when it comes to interpreting the resulting data, a less experienced analyst could run into problems. Crude plant extract contains a huge number of chemical constituent which may be likely to co-elute in a chromatography spectrum. If the peaks of this spectrum are misread, it can lead to the incorrect reporting of cannabinoid content for the product in question. This discrepancy could be highly problematic if the product is being sought specifically for the action of certain cannabinoids, as is common for medicinal use.
Selection ion monitoring (SIM) LC/MS analysis for this kind of potency testing has been proposed by the authors as a potentially advantageous application here for the industry. SIM LC/MS, which monitors only the protonated molecules of the targeted cannabinoids of interest, is highly selective and could be a good solution to this challenge. The authors also note that using some other liquid chromatography method, such as ultra-high-performance liquid chromatography (UHPLC), could also go some way towards improving the separation efficiency, but that the limited sensitivity of the PDA detector would likely still cause the same problem with differentiation. LC/MS or SIM LC/MS then remain promising avenues for future investigation.
Application 2: Pesticide Testing
Medicinal cannabis products are often used by people who may be immunocompromised in some way. So, while residual pesticides may have unpleasant consequences for recreational consumers, but for the medicinal user it could have drastic and potentially life-endangering effects.
The example the review authors give is that of the fungicide myclobutanil. While it is regarded as safe for general use on other crops such as almonds, strawberries and grapes, it presents a huge risk if used on cannabis. When heat is applied — as would be the case when cannabis is smoked via cigarette — myclobutanil is converted into the very highly toxic gas, hydrogen cyanide. For reasons such as this, it is important that the analytical techniques applied to pesticide testing are as comprehensive as possible, and are able to detect pesticide traces even at a concentration of only several parts per billion (ppb).
Here, they say, mass spectrometry could be of use as methods such as SIM LC/MS allow for the determination of unknown compounds at the mid-to-low ppb range, with other MS techniques like LC/MS/MS capable of detecting even very low ppb levels of compounds in the complicated plant matrix. This is already being recognized by some state regulators who are now including LC/MS/MS as one of their approved methods for the detection and measurement of pesticides in medical marijuana.
Besides these two avenues, the authors of the review also suggest that mass spectrometry could be applied to terpene determination, forensic toxicology, identification of origin of growth, and the detection of contaminants such as heavy metals, residual solvents, microbial infection, and mycotoxins.
“Going forward, it will be important to assure users of [cannabis] products that safe, accurate levels of expected active ingredients are present as well as to assure them that unsafe chemicals including pesticides, mycotoxins, and heavy metals are absent,” write the review authors. “We suggest [mass spectrometry] should be used more widely in the future to provide the superior combination of selectivity and sensitivity demanded by the chemical complexity and diversity of the plant and the many products likely to be produced from it.”
From a perspective of consumer trust, and also acceptance of the cannabis industry as a whole in society, it will be important that the industry maintains a good safety record free from preventable adverse events. Experimenting with the use of analytical methods, such as mass spectrometry, that have been tried and tested in other highly scrutinized industries may be a good way to demonstrate that commitment to safety and best practice. It may be the case that pre-existing methods are already perfectly satisfactory in terms of performance, but as the old adage goes, “nothing ventured, nothing gained.”