An Enhanced LC-MS/MS Technique for Distinguishing Delta(8)- and Delta(9)-Tetrahydrocannabinol Isomers in Blood and Urine Specimens

Among the abundance of cannabinoids identified in cannabis, the active parent drug, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), and its oxidized metabolite, 11-nor-9-carboxy-Delta(9)-THC (Delta(9)-THCCOOH), are attractive analytical targets to detect cannabis use. More recently, confirmation of these analytes may be hindered by a related interfering compound. Forensic toxicology laboratories attribute this phenomenon to an increase in cases containing Delta(8)-tetrahydrocannabinol (Delta(8)-THC) and 11-nor-9-carboxy-Delta(8)-THC (Delta(8)-THCCOOH). It is technically challenging to chromatographically resolve and accurately quantify Delta(8)- and Delta(9)-THC and THCCOOH in toxicology specimens due to their structural resemblance. This study describes a validated method to resolve and quantify active Delta(8)-THC and Delta(9)-THC in blood while qualitatively confirming the inactive metabolites Delta(8)-THCCOOH and Delta(9)-THCCOOH in blood and urine. Analytes are extracted and concentrated by solid-phase extraction and analyzed by liquid chromatography electrospray ionization tandem mass spectrometry, which is amenable to modern toxicology laboratory routine workflows. This procedure offers a clear solution to untangling mixtures of these isomers, particularly in cases where Delta(8)-THC and its metabolite are the sole or dominant form.