HPLC-UV quantitation of synthetically derived THC, THCP, and HHC isomers in commercial vaping liquids and edibles (2019-2024).

Abstract

Synthetically derived tetrahydrocannabinol (THC) products, including vaping liquids and edibles, are widely available in the US. Serious adverse events associated with the use of THC products are reported in large-scale studies for both adults and children and include intoxication, psychosis, encephalopathy, CNS depression, respiratory failure, and acute cardiovascular emergencies. Between 2019 and 2024, a variety of synthetically derived "Δ⁹-THC" and "Δ⁸-THC" products were submitted for quantitative THC analysis. The products contained various combinations of seven positional THC isomers: Δ⁹-tetrahydrocannabinol (Δ⁹-THC), Δ⁸-tetrahydrocannabinol (Δ⁸-THC), Δ^6a10a-tetrahydrocannabinol (Δ^6a10a-THC), Δ¹⁰-tetrahydrocannabinol (Δ¹⁰-THC), Δ⁴⁽⁸⁾-iso-tetrahydrocannabinol (Δ⁴⁽⁸⁾-iso-THC), Δ⁸-iso-tetrahydrocannabinol (Δ⁸-iso-THC), and exo-tetrahydrocannabinol (exo-THC). Several products contained THC isomers in combination with tetrahydrocannabiphorols (THCPs) or hexahydrocannabinols (HHCs). A series of quantitative high-performance liquid chromatography-ultraviolet detection (HPLC-UV) methods for THCs, THCPs, and HHCs was developed and validated. The methods use ACE Excel mixed C18-aromatic 3.0-micron or Cosmocore/Cosmosil cholesterol-ligand-based 2.6/2.5-micron columns. Optimized resolution for the THC isomers was obtained using ternary mobile phases containing methanol, acetonitrile, and acetic acid buffer and a 45°C column temperature. Representative data for synthetically derived cannabinoid products analyzed over a five-year period are provided. Total THC isomer contents for vaping liquids and dabs ranged from 25 to 96% w/w. Total THC isomer contents for gummies and other candies ranged from 57-321 mg/gummy or 13-24 mg/candy piece, respectively. The highest amount of cannabinoids was found in a THC/HHC combination product with a Δ⁸-THC content of 649 mg/gummy and a total combined THC/HHC isomers content of 791 mg/gummy.