The transition of cannabis from an illegal drug to a drug for medical and even recreational use raises challenging questions for regulatory agencies and analytical chemists alike. Here, we show a selection of analytical techniques based on compact mass spectrometry (MS) in combination with three different sample inlets (atmospheric solids analysis probe, thin-layer chromatography [TLC], and classical liquid chromatography [LC]) for the detection and quantification of cannabinoids and pesticides in cannabis-related material and contraband.
In the United States, cannabis is now on its way to become a normal crop and consequently many of the currently discussed challenges that relate to cannabis and its products have long been solved for other comparable crops. What makes cannabis unique though, and significantly more complicated, is its currently fragmented legal status as well as its various forms of consumption and aims. Is it a medicine or a recreational drug? Is it a tobacco product? Is it food? Does it have parallels to alcohol? Such questions should ultimately be answered and will dictate how it will be regulated in the marketplace and what agency should be responsible for its monitoring.
One of the issues with cannabis that is often overlooked is the changing cannabinoid make up over the last decades. Cannabis produces upward of 400 compounds (approximately 80 compounds unique to this plant) that interact to varying degrees on the natural cannabinoid receptors in the human brain as well as the nervous and immune system (the endocannabinoid system ). Unfortunately, cannabis strains with extremely high psychotropic tetrahydrocannabinol (THC) levels have been bred in the past for illegal recreational drug use (some reports show cannabis strains with THC content as high as 30-40% ). But those strains have little benefit for medicinal use because their potent psychotropic effect is undesirable for patients and because other cannabinoids, terpenes, and secondary plant metabolites such as cannabidiol (CBD) are down-regulated at the same time and these are likely much more important for medicinal effects (3,4).
Another emerging problem is the contamination of the cannabis product with pesticides. Because of its status as illegal drug on the federal level there is no United States Environmental Protection Agency (US EPA) guidance as to what pesticide can be used during the growth of the plant or what residue level would be acceptable (and monitored by the Food and Drug Administration [FDA] or the U.S. Department of Agriculture [USDA]). Consequently, it is illegal to use any pesticides on cannabis plants and it should be an organically grown product (5). However, a test analysis of a very small number of cannabis samples from dispensaries in Los Angeles, California, in 2009 showed that two out of three samples had significant levels of the insecticide bifenthrin—one sample exceeded the legal limit for an edible crop by a factor of 1600 (6).
It is noteworthy that the major consumption of cannabis is through smoking—not ingestion—and it has been shown that pesticides can pass into the mainstream smoke at rates up to 69%, depending on smoking style (filter or filterless, waterpipe and so on) (7). In other words, two of the three samples obtained in the above small-scale study would be considered a consumer health risk. This is even more concerning in light of patients with compromised immune systems taking medical cannabis to improve their health status.
Finally, it is important to note that despite changes in some states, cannabis is still an illegal drug in a majority of states and on the federal level. The challenges described above can of course be monitored with analytical chemistry workflows that satisfy the different requirements for
- simple and legally defensible cannabis detection in contraband material;
- detection of pesticides and their quantification;
- and characterization of the major cannabis components to provide adequately labeled products that informed consumers can choose from where it is legal to do so.
Here, we discuss three analytical workflows based around compact mass spectrometry (MS) with different sample inlet systems ranging from the more recent atmospheric solids analysis probe (8), a thin-layer chromatography (TLC) extraction device, and a more classical high performance liquid chromatography (HPLC) inlet to demonstrate cost effective and easy-to-use solutions for law enforcement, producers, and dispensaries of cannabis.
Atmospheric Solids Analysis Probe and Compact MS Analysis of Contraband Material and Surfaces of Interest
The glass capillary of the atmospheric solids analysis probe (ASAP, Advion, Inc.) was either placed into direct contact with the contraband material or rubbed over the index finger or shirt sleeve of a volunteer that had been in contact with the material. The capillary was then placed into the source housing holder with commencement of MS acquisition. The sample inlet (Figure 1) uses hot nitrogen gas to rapidly vaporize the analytes present on the tip of the glass capillary and transports the vapor stream to a corona discharge needle where molecules are ionized by atmospheric pressure chemical ionization (APCI). (See upper right for Figure 1, click to enlarge, caption: Figure 1: Schematic of the ASAP ion source inlet as deployed on a single-quadrupole compact mass spectrometer (expression, Advion Inc.) Ions are transferred into the MS analyzer through the inlet capillary of the mass spectrometer. With this technique the separation of analytes happens exclusively during the evaporation stage and by mass-to-charge ratio in the gas phase.
TLC and Compact MS Analysis of Cannabinoids
Cannabinoid standards and a make-up sample of a leaf extract fortified with cannabinoids were separated on TLC silica gel 60 F254 (Merck) with a developing solvent of 80:20 petroleum ether (60-80 bp)-dioxane (Sigma Aldrich). The TLC-compact MS analysis used a Plate Express (Advion, Inc.) extraction device with a 200-µL/min solvent flow of methanol-0.1 vol% formic acid and an extraction head with an area of approximately 1 mm × 2 mm.
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