Development and validation of an assay to measure cannabidiol and Δ9-tetrahydrocannabinol in human EDTA plasma by UHPLC-MS/MS

The therapeutic use of cannabinoids has increased with providers often recommending cannabinoid-containing products with limited pre-clinical and clinical pharmacokinetic studies. An ultra-performance liquid chromatography with triple quadrupole mass spectrometry method was developed and validated for the determination of cannabidiol and Δ9-tetrahydrocannabinol in human ethylenediaminetetraacetic acid (EDTA) plasma. The cannabinoids are extracted from plasma with a liquid-liquid procedure utilizing methyl tert-butyl ether. UHPLC Separation was achieved with a Waters Acquity HSS T3 column (100 × 2.1 mm, 1.8 μm) under isocratic conditions (18:82:0.02 water:methanol:formic acid v/v/v). The run time was 8.5 min. Detection of analytes was achieved using electrospray ionization and triple quadrupole selected reaction monitoring. Standard curve concentrations ranged from 0.5 to 250 ng/mL for cannabidiol and Δ9-tetrahydrocannabinol. The intra- and inter-day accuracy (% bias) and precision (relative standard deviation) were <9.20% in low, medium, and high quality control samples. The validated method was applied to the analysis of donated human EDTA plasma. The assay provides an important patient monitoring capability to determine variability in clinical pharmacokinetics during use of cannabinoid-containing products.