Heavy metals are some of the most important contaminants to test for in cannabis analysis. Many heavy metals, such as arsenic, mercury, and lead, can be introduced into the cannabis plant—and therefore the flowers—through cultivation in contaminated soil. Heavy metals can also be introduced later on in the manufacturing process from contaminated processing equipment or raw materials. Because of the health risks associated with these metals, it is imperative that they are detected before entering the market place. This article discusses a robust method for identifying heavy metals in cannabis samples, using inductively coupled plasma-mass spectrometry (ICP-MS). It also highlights the importance of sample preparation methods that can be applied to a wide range of cannabis products. Both will help scientists and technicians better understand how to uncover contamination and help protect consumers from harm.
Numerous studies have identified that cannabis and hemp plants are active accumulators of heavy metals from the soil and water they grow in, which have been contaminated through anthropogenic activities such as mining and smelting (1). Concentrations of these heavy metals are in the parts per billion (ppb) or parts per trillion (ppt) region. Although considered to be at a trace level, the heavy metals may still cause harm to consumers and would therefore require sensitive testing capabilities.
As the use of legalized cannabis across many forms and products continues to increase, it is also critical that robust methods are likewise developed to detect and quantify trace levels of these heavy metals. This is particularly important for long-term users of cannabis products, including patients that may have compromised immune systems or use cannabis-based medicine products because heavy metals can accumulate in the body and cause serious harm (2).
Furthermore, because regulatory limits for heavy metals can vary between jurisdictions and more elements and lower limits are being added to regulations all the time, it is essential that laboratories leverage methods of detection that have the flexibility and sensitivity required for this fast-changing industry.
For example, Canada and U.S. states such as California, Oregon, and Colorado have published limits for heavy metals. Though regulations can vary between geographic regions where cannabis is permitted, many of the set limits are based on United States Pharmacopeia (USP) “General Chapter <232>” guidance (3). The key metals of interest are cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg). These heavy metals fall within the U.S. Food and Drug Administration (FDA) Class 1 category for substances that are toxic to humans with use allowed in the manufacture of pharmaceuticals (4). Table I provides a list of heavy metal limits based on jurisdiction and route of administration.
To help combat the issues surrounding the frequent prevalence of heavy metals in cannabis, inductively coupled plasma-mass spectrometry (ICP-MS) can be used for trace metal analysis. ICP-MS provides effective detection limits for elemental impurities down to ppb or ppt levels.
The technology works by combining a high temperature ICP source and a mass spectrometer. Samples are introduced into an argon plasma as aerosol droplets, which are dried, dissociated into atoms, and then ionized. Quadrupoles are often used to rapidly scan the mass range with one mass-to-charge ratio being allowed to pass through the mass spectrometer at a given time. The number of ions hitting the detector for a given mass is related to the concentration of the element in that sample (5).
In comparison to other techniques such as inductively coupled plasma-optical emission spectrometry (ICP-OES), ICP-MS can achieve greater sensitivity and many orders of magnitude, enabling a reduction in the amount of sample required. The greater sensitivity is ideal for the determination of trace metals in cannabis samples since the usual levels for some analytes are extremely low (sub-ppb).
The analysis of heavy metals in cannabis remains challenging because of the low level of contaminants in complex matrices, the wide variety of cannabis types, and homogeneity issues that can exist in certain samples. Cannabis flowers are a natural, heterogeneous substance that must be homogenized prior to preparation. When a sample is heterogeneous, say in cannabis brownies or gummy bears, the concentration of heavy metals can vary widely within the sample and the accuracy of analysis is reduced. Though the process of homogenization ensures consistency within the sample, it can also introduce contamination. It is, therefore, vital that preparation protocols are produced that can effectively homogenize cannabis samples while avoiding contamination. The homogenization of cannabis flowers is particularly challenging because the sample requires an optimal digestion protocol to ensure that there are no particulates left in the final digest state.
- D.V. Gauvin, Z.J. Zimmermann, J. Yoder, and R. Tapp, Pharm. Regul. Aff. 7(1), 199 DOI: 10.4172/2167-7689.1000202 (2018).
- M. Jaishanker, T. Tseten, N. Anbalagan, B.B. Matthew, and K.N. Beeregowda, Interdiscip. Toxicol. 7, 60–72. DOI: 10.2478/intox-2014-0009 (2014).
- General Chapter <232> “Elemental Impurities in Pharmaceutical Materials– Limits,” 2nd supplement to United States Pharmacopeia 39–National Formulary 34 (USP39–NF34) (United States Pharmacopeial Convention, Rockville, Maryland, 2016). Updates published in Pharmacopeial Forum 42(2).
- FDA Pharmaceutical Quality Resources – Elemental Impurities, July 2018 https://www.fda.gov/drugs/pharmaceutical-quality-resources/elemental-impurities (Accessed on August 14, 2019).
- PerkinElmer Technical Note, “The 30 minute guide to ICP-MS,” https://www.perkinelmer.com/lab-solutions/resources/docs/TCH-30-Minute-Guide-to-ICP-MS-006355G_01.pdf (Accessed on August 14, 2019).
- PerkinElmer Technical Note, “All matrix solution system for NexION ICP-MS platforms,” https://www.perkinelmer.com/lab-solutions/resources/docs/TCH_NexION-AMS-System_013224_01.pdf (Accessed on August 14, 2019).
- General Chapter <233> “Elemental Impurities in Pharmaceutical Materials – Procedures,” 2nd supplement to United States Pharmacopeia 38–National Formulary 323(USP38–NF33) (United States Pharmacopeial Convention, Rockville, Maryland, 2015).
- Emerald Scientific, “The Emerald Test: How it works,” https://pt.emeraldscientific.com/howitworks/ (Accessed on August 14, 2019).
Aaron Hineman is the Inorganic Product Line Leader, Americas at PerkinElmer in Blaine, Washington. Toby Astill is the Global Market Manager – Cannabis & Hemp Markets at PerkinElmer in Downers Grove, Illinois. Direct correspondence to: [email protected] and [email protected]
How to Cite This Article
A. Hineman and T. Astill, Cannabis Science and Technology 2(5), 66-70 (2019).