Certified Reference Materials and Internal Standards for Cannabinoid Analysis

The quantitative power of an analytical method is often measured by the quality and performance of the reference standard. This is true in many applications including the analysis of cannabinoid concentrations in cannabis extracts by means of HPLC, LC-MS, and other techniques.

Companies such as Cayman Chemical and others offer a wide range of certified reference standards for natural and synthetic cannabinoid compounds, suitable for applications ranging from research to forensic testing.

Compounds with Certified Reference Material (CRM) in the name are highly qualified materials manufactured and tested to meet ISO/IEC 17025 and ISO Guide 34 international guidelines for reference materials. These materials are tested using validated analytical methods on qualified instrumentation to ensure traceability to SI units of measure.

Companies like Cayman state their CRMs are tested for Homogeneity and Stability and are provided with a certificate stating the CRM property value(s) along with the combined uncertainty of the property value(s). They further state these materials are intended for quantitative applications where quantitative accuracy and uncertainty are critical.

To further explore Cayman, the website lists 36 cannabinoid products. The Phytocannabinol Mixture 1 product is a mixture of 10 common cannabinoids of interest, and is meant to provide high quality standards for HPLC-UV, GC-MS, LC-MS, and GC-FID analysis. The ≥98% pure mixture contains Δ9-THC, Δ8-THC, Tetrahydrocannabinolic Acid, Cannabinol, Cannabidiol, Cannabidiolic Acid, (±)-Cannabichromene, Cannabigerol, Cannabigerolic Acid, and Cannabidivarin. Phytocannabinoid Mixture 10 is also listed offering a larger total amount of standard per sample. Individual cannabinoid standards are listed as well, including: Δ9-Tetrahydrocannabinol (THC), Cannabigerol (CBG), and Cannabidiol (CBD), among a multitude of others.

Many of the products are offered as CRMs however all of these cannabinoids are restricted products, controlled substances that require special processing and license verification. The buyer must have a current U.S. DEA Analytical or Researcher Controlled Substance Registration for domestic sales. This same policy applies to any company offering cannabinoid compounds for sale as reference or research materials.

Exempt preparations are also available for use as internal standards in analytical instrumentation such as GC and LC-MS. As an example, the Δ9-THC-d9 product from Cayman contains 9 deuterium atoms on the pentyl group of THC. The resulting shift in molecular weight is suitable for mass spec quantitation, as the peaks of the internal standard and the analyte can be clearly resolved without impacting the structure and behavior of the core molecule. This compound is exempt from certified status and formulated to meet criteria established by the US DEA – as such DEA registration and licensure is not required for purchase. The same holds true for the other exempt internal standards listed.

As the cannabis industry matures, analytical testing labs with have a greater need for quality reference materials and internal standards for cannabinoid identification and potency testing. Tools like those detailed above may find expanded use beyond forensics and research applications, and help drive the quality control and GMP aspects of cannabis processing and testing.