Background
Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmaco- and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids.
Methods
To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11OH-THC), 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol (CBN), cannabidiol (CBD), cannabigerol (CBG), cannabidivarin (CBDV), Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma.
Results
In contrast to atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI) was associated with extensive ion suppression in plasma and urine samples. Thus, the APCI assay was validated showing a lower limit of quantification (LLOQ) ranging from 0.39 to 3.91 ng/mL depending on study compound and matrix. The upper limit of quantitation (ULOQ) was 400 ng/mL except for THC-C-gluc with a ULOQ of 2000 ng/mL. The linearity was r> 0.99 for all analyzed calibration curves. Acceptance criteria for intra- and inter-batch accuracy (85%-115%) and imprecision (<15%) were met for all compounds. In plasma, the only exceptions were THCV (75.3%-121.2% inter-batch accuracy) and CBDV (inter-batch imprecision, 15.7%-17.2%). In urine, THCV did not meet predefined acceptance criteria for intra-batch accuracy.
Conclusions
This assay allows not only for monitoring THC and its major metabolites, but also of major cannabinoids that are of interest for marijuana research and clinical practice.