A Validated Method for the Detection of Δ9-Tetrahydrocannabinol and 11-nor-9-Carboxy-Δ9-Tetrahydrocannabinol in Oral Fluid Samples by Liquid Chromatography Coupled with Quadrupole-Time-of-Flight Mass Spectrometry

A quantitative liquid chromatography-electrospray ionization-quadrupole-time-of-flight (TOF) mass spectrometry (MS) method for simultaneous determination of Δ9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in oral fluid samples was developed and fully validated. The analytes were isolated from the oral fluid by classic liquid-liquid extraction. The two compounds were separated in 9.5 min with a total analysis time of 19 min. The linear dynamic range was established from 0.1 to 100 ng/mL for THC and 0.5–100 ng/mL for the THC-COOH. The method had a good intra- and interassay accuracy and precision at each measured concentration. No matrix effects were observed for the analytes or the labeled internal standards. Accurate mass measurement was achieved to ± 5 ppm. The sensitivity of the method results from a combination of unique chromatographic retention time, the use of MS-MS, and the “exact mass” measurement of the target ions by a TOF analysis. The method was successfully applied to two types of oral fluid samples. One type was collected from roadside driving-under-the-influence studies. The second was used to assess the recovery of the THC from an oral fluid collection device under laboratory conditions. Although the use of the TOF MS in the forensic and toxicology fields is not as widespread as the triple-quadrupole technology, it offers some significant analytical advantages that are demonstrated by this method.