Quantification of psychotropic cannabinoids in newly emerging hemp-derived products and evaluation of their stability and interconversion during storage

Since the 2018 Farm Bill excluded hemp from the statutory definition of cannabis with a Δ9-THC (tetrahydrocannabinol) concentration not more than 0.3%, psychotropic cannabinoids other than Δ9-THC, which are double-bond position isomers, homologues and analogues of Δ9-THC, including Δ8-THC, Δ10-THC, THCP (tetrahydrocannabiphorol), THC-O-acetate, HHC (hexahydrocannabinol), and HHC-O-acetate, have been sold online and by brick-and-mortar retailers across the U.S., based on legal arguments that the 2018 Farm Bill legalized them due to their natural presence in hemp, despite in amounts too small to produce psychotropic effects, and/or because they are derived from CBD (cannabidiol) that are legally extracted from hemp. The ever-increasing marketing of psychotropic cannabinoids in newly emerging hemp-derived products has made it clear that their contents must be accurately measured and their stability and interconversion during storage should be clearly understood so that State and federal regulators can make informed decisions for a better regulated hemp market.

Double-bond position isomers of Δ9-THC are produced by non-specific isomerization reactions of CBD, resulting in a mixture probably containing D8-THC, D9- THC, D10- THC, Δ11- THC, Δ6a,10a- THC, Δ6a,7- THC, Δ7-THC, CBD, CBC (cannabichromene), CBL (cannabicyclol) and CBT (cannabicitran). Their quantification requires baseline separation of all eleven isomers because their differentiation using a triple quadrupole was proven unachievable by us, which is a significant challenge because even the baseline separation of Δ8-/Δ9-THC was not achieved by many published methods. So far, the maximum number of cannabinoids that have been baseline separated was twenty by us, including D8-THC, D9-THC, CBD, CBC, CBL and CBT. With this project, a LC-DAD-ESI/MS/MS methods using a high-resolution mass spectrometer will be developed after a systematic separation optimization using four carefully selected LC columns with varying selectivity towards cannabinoids. The optimized method will be further applicable for the quantification of homologues and analogues of Δ9-THC due to larger structural and mass differences. The method will be easily adopted by crime laboratories with different instrumentation because it will be easily dissected after our comprehensive study, e.g., a LC-UV method using a traditional UV detection, a LC-ESI/MS method using a single quadrupole, or a LC-ESI/MS/MS method using a triple quadrupole.

The stability of psychotropic cannabinoids, including Δ9-THC, during storage has not been well studied so far. This project further seeks to understand the reaction kinetics of psychotropic cannabinoids during chemical degradation. It will provide valuable information about the shelf-life of psychotropic cannabinoids under different storage conditions. CA/NCF