Cannabis: A messy matrix for method development

To consistently and effectively analyze cannabis, labs must develop and validate many different analytical methods. Covering all the required analysis—such as potency, pesticide testing and residual-solvent analysis—necessitates multiple methods. Plus, the sample matrix itself presents unique challenges.
When asked about the key challenges of method development and validation for cannabis testing, Eric Wendt, Chief Scientific Officer at Green Leaf Lab, says, “There are a lot of answers to that question. One is making methods that accommodate all of the matrices, such as the flowers, concentrates and the vast and ever changing cannabinoid product category.”
To manage the variety of cannabis matrices, analytical methods usually include sample preparation that cleans up the matrix. “Keeping the instruments cleaner extends how many samples can be tested before maintenance,” Wendt explains. “We need methods that can run about 100 samples before maintenance to be efficient.”
After that, the analysis at hand determines the necessary instrumentation. When testing for pesticides, for example, Adam Hamdani, a method development chemist at Green Leaf Lab, points out that “you can’t test for all of the required compounds on one instrument.” Some pesticides require liquid chromatography with triple-quadrupole mass spectrometry (LC-MS/MS), and others require gas chromatography (GC-MS/MS) to properly analyze at the parts-per-billion detection requirements.
In thinking about what goes into a method and what comes out, scientists need to weight the options. “Like other quality control labs,” Wendt explains, “it’s a balance of throughput, sensitivity and time.”
Breaking trail
Part of the challenge comes from starting from scratch. A spokesperson from Yofumo Technologies , says, “Some of the key challenges of method development and validation for cannabis testing include the lack of high quality reference standards and a lack of direction to follow.” For example, cannabis includes more than 60 kinds of cannabinoids, but labs that lack a U.S. Drug Enforcement Agency license can only purchase reference standards for about a dozen of the cannabinoids.
A lack of federal regulation compounds the challenges. As explained by Yofumo, “While pharmaceutical laboratories clearly know to follow FDA rules and guidelines and environmental laboratories clearly know to follow EPA guidelines, cannabis testing laboratories lack a clear and direct approach.” That leaves labs to create their own guidelines, and they won’t do it the same way.
Protecting your investment
When I ask Wendt if labs share their methods, he says, “At the moment, it’s fairly proprietary, because there’s no universal method and it’s a fairly competitive space.” That’s easy enough to understand, because an analytical lab makes significant investments in equipment, scientists and time to develop and validate methods. No one will just give that away.
That said, Wendt points out that Green Leaf Lab is open to collaboration and discussion.” For instance, Green Leaf Lab provided data and some methodology that Agilent Technologies used to show how its instruments can be used in cannabis labs.
In the future, standardization will evolve. “If everyone is running the same methods and a universal standard is set between states, then you are setting the groundwork for a national economy for cannabis,” Wendt explains. That will probably only happen in the United States with federal legalization.