Validation of a liquid chromatography-tandem mass spectrometry method for analyzing cannabinoids in oral fluid

A liquid chromatography tandem mass spectrometry method was developed for quantifying ten cannabinoids in oral fluid (OF). This method utilizes OF collected by the Quantisal™ device and concurrently quantifies cannabinol (CBN), cannabidiol (CBD), Δ⁹-tetrahydrocannabinol (THC), 11-hydroxy-Δ⁹-THC (11-OH-THC), 11-nor-9-carboxy-Δ⁹-THC (THC-COOH), 11-nor-9-carboxy-Δ⁹-THC glucuronide (THC-COOH-gluc), Δ⁹-THC glucuronide (THC-gluc), cannabigerol (CBG), tetrahydrocannabiverin (THCV), and Δ⁹-tetrahydrocannabinolic acid A (THCA-A). Solid phase extraction was optimized using Oasis Prime HLB 30 mg 96-well plates. Cannabinoids were separated by liquid chromatography over a BEH C18 column and detected by a Waters TQ-S micro tandem mass spectrometer. The lower limits of quantification (LLOQ) were 0.4 ng/mL for CBN, CBD, THC, 11-OH-THC, THC-gluc, and THCV; and 1.0 ng/mL for THC-COOH, THC-COOH-gluc, CBG and THCA-A. Linear ranges extended to 2000 ng/mL for THC and 200 ng/mL for all other analytes. Inter-day analytical bias and imprecision at three levels of quality control (QC) was within ±15%. Mean extraction efficiencies ranged from 26.0-98.8%. Applicability of this method was tested using samples collected from individuals randomly assigned to smoke either a joint containing <0.1%, 5.9%, or 13.4% THC content. This method was able to identify and calculate the concentration of 6 of 10 cannabinoids validated in this method.