The cannabis revolution presents a wide range of challenges for analytical chemists. This is compounded by the lack of support from organizations such as the FDA, EPA, and Department of Agriculture. Without strong guidance from federal agencies, the states and foreign countries are forced to create their own programs to ensure public safety. PerkinElmer has emerged as a thought leader in this niche area and is focused on creating targeted solutions that address the health concerns associated with the legalization of cannabis.
Recently, I had a chance to interview Dr. Kaveh Kahen (general manager of mass spectrometry) and Dr. Feng Qin (software product manager) of PerkinElmer, Inc. (Woodbridge, Ontario, Canada), about PerkinElmer’s involvement in the rapidly emerging market of cannabis analysis.
RLS: In March, 2016, PerkinElmer hosted a seminar in Concord, CA, focused on the analysis of cannabis. What has happened since then?
KK: Cannabis products for medical purposes are gaining public recognition and support, and more states are moving toward legalizing cannabis for either medical or recreational purposes. The recreational market is lagging somewhat, but where it is legalized, it shows signs of being even larger than the medicinal segment. PerkinElmer has both the specialized instrumentation and experience needed to help our customers meet the analytical demands of these challenging applications. Moreover, we are developing turnkey solutions that should facilitate getting consistent results.
Figure 1 – NexION 2000 ICP/MS.RLS: What are these analytical needs?
KK: Starting at the farm level, our NexION 2000 ICP/MS (Figure 1) is ideal for measuring heavy metals, which are potentially toxic in irrigation water and soil. Following on this, many plants are known to accumulate metals in concentrations that are often several orders of magnitude higher than that of the surrounding environment and, therefore, there is a need to accurately quantify these toxic metals. This application is especially useful in scenarios where cannabis farms are established on repurposed land or old sites that have elevated levels of Pb or As from peeling paint. Assured safety is one of the expected results of ethical cannabis growing.
RLS: Interesting. Can you to talk about residues of pesticides or herbicides?
KK: Pesticide residue is an obvious concern, especially from plants grown without formal protocols in facilities that were designed for purpose. We have decades of experience analyzing pesticide and herbicide residue by GC/MS and LC/MS. We are working with multiple stakeholders with various roles in the supply chain for the legal and ethical cannabis market to develop turnkey solutions that meet the applicable requirements. Over time, we expect the lists of analytes to grow and include the most common pesticide, biocide, and environmental analytes. Plus, state agriculture departments can lead growers to use the most effective products and safe application protocols. Recent reports have found that some pesticide residues are preferentially extracted compared to the cannabinoids and terpenes. This may be a new cause for concern.
RLS: I’ve heard about problems with high humidity in the grow or dry buildings leading to danger from mycotoxins.
KK: Yes, growers try to optimize production by controlling humidity, temperature, light level, and CO2 partial pressure. Despite this, wet spots can exist, or temperatures may not be optimal, leading to the growth of mold or fungus. Mycotoxins are a group of chemicals that are produced by mold or fungus. They are highly toxic and, consequently, residue levels should be carefully regulated.
PerkinElmer has decades of experience in the HPLC analysis of plants and food products for aflatoxins. We recently developed a new method using LC-MS/MS technology to determine trace levels of aflatoxins in food. This method can be further optimized for cannabis analysis. We anticipate that the monitoring of various THC extracts for toxins will be generally required.
RLS: What do you recommend for terpenes? Next to THC content, terpene content is a critical quality attribute, correct?
FQ: Yes, terpenes are important and vary greatly within particular cultivars. Producers test terpene profiles to ensure lot-to-lot consistency. Some growers may use terpene contents to guide plant breeding. Due to the chemical and physical nature of terpenes, these types of analysis are done by GC/MS and LC/MS.
RLS: What about residual solvents in extracts?
KK: This is an area where GC-headspace analysis is an excellent fit. PerkinElmer has been a market leader in headspace analysis (for example, those needed for blood alcohol levels). Similar analysis can be done for light hydrocarbons such as propane, butane, or hexane. CO2 is different. The amounts are small and CO2 is classed as GRAS (generally recognized as safe), so the need for this assay is low.
RLS: What about potency?
KK: Medicinal marijuana covers several nonpsychoactive cannabis compounds, including diol and acid. Recreational uses generally focus on THC content. HPLC is usually the method of choice for potency analysis.
RLS: What about impairment or under influence similar to blood alcohols?
KK: This is a real, unsolved problem. It is difficult to establish a clear relationship between a person’s THC levels in blood and impairment. Additionally, concentrations of THC and its metabolites depend on patterns of usage and dosage. Consequently, there is a real need for a comprehensive study on dose–response relationships. Once a protocol for determining impairment has been established, we can offer relevant instrumentation and assay protocols. However, one major problem is that the THC levels in blood decrease rapidly after using cannabis and may very well be below the detection limits of the most sensitive benchtop instruments, even while the person is technically impaired.
RLS: Let’s return to the instruments that PerkinElmer offers for assays of cannabis. These include GC, GC/MS, LC, LC/MS, and ICP/MS—technologies that require experience and care to utilize. How can PerkinElmer make these instruments useful to operators who have little scientific training or interest?
FQ: We anticipate that labs involved early in the cannabis-testing segment will have technical proficiency covering the decile spectrum, from very low to very high. The challenge is that society often has little insight in evaluating technical competency. To this end, PerkinElmer will design software to anticipate problems and implement mitigation protocols, including work-arounds. We have a broad customer base in GC, LC, GC/MS, LC/MS, and ICP/MS and a very good understanding of their needs. Our software development efforts are focused on developing complete solutions that guide the operator through the entire workflow of developing the methods, running the samples, processing data, and generating reports.
Figure 2 – QSight LC-MS/MS system.RLS: Tell me more about the methods that you are developing. Will they resemble the detailed protocols similar to USP or ASTM?
FQ: The method we have developed is specifically for pesticide residue analysis based upon the Oregon regulation. We used the PerkinElmer QSight LC-MS/MS system (Figure 2) to analyze 59 pesticides in cannabis flowers and concentrates. The method involves QuEChERS sample preparation, UHPLC separation, and MS/MS detection. This enables users to analyze both GC and LC amenable pesticides in one run. Stayclean technology, which is implemented in our mass spectrometer, greatly reduces the necessity for instrument cleaning and maintenance, making this method suitable for dirty matrices, such as those found in cannabis flower and concentrates. The method follows typical food-contaminant analysis protocols that are recognized by regulatory bodies.
RLS: PerkinElmer offers a wide range of technologies for cannabis assay. A typical laboratory in a permissive state could possess several instruments, including an HPLC, GC, and ICP/MS. Will these have a common human interface? Or even market-segment specific instruments and software such as CANLab (Accurate Technologies, Novi, MI)?
FQ: In general, our goal in software development is to offer common or at least similar user interfaces wherever it is possible to facilitate our customers’ transition from one platform to another with minimal training. As the cannabis market grows, we will be considering targeted “vertical applications” for this market that will be embedded in different instrument platforms but will follow a very similar workflow and common user interface.
Robert L. Stevenson, Ph.D., is Editor Emeritus, American Laboratory/Labcompare; email: [email protected].