Ultra-sensitive analytical methodology for the quantification of 11-nor-9-carboxy-THC (THC-COOH) in oral fluid

Using the SCIEX Triple Quad™ 7500 LC-MS/MS System – QTRAP® Ready, powered by SCIEX OS Software

Pierre Negri1 and Ian Moore2


The SCIEX Triple Quad 7500 System is a robust quantitative platform with exceptional performance in speed, linear dynamic range and sensitivity for the accurate quantification of THC-COOH in oral fluid. The increased selectivity of MRM3 provided a 5 fold increase in sensitivity of detection over MRM analysis due to the enhanced selectivity of the method. 

12617 7500


With over 192 million consumers worldwide in 2018, cannabis is the most commonly abused recreational drug.1 Detection of its use can be performed in several biological matrices such as blood, urine, hair and oral fluid. In recent years, oral fluid has gained considerable attention as a quicker and less invasive means of monitoring cannabis use. More specifically, the use of this matrix for drug testing benefits from ease of sampling, observed collection and difficulty of sample adulteration. 

Δ9-tetrahydrocannabinol (THC) has previously been used as the marker of choice to monitor cannabis consumption. However, the detection and quantification of THC in drug screening can result in a high-number of false positives since this analyte can be found in subjects passively exposed to cannabis. 11-nor-9-carboxy-THC (THC-COOH) was proposed as a marker of cannabis intake since it is not detected in oral fluid collected from subjects passively exposed to cannabis.2 The low (pg/mL) concentrations of THC-COOH in oral fluid of active users together with the abundance of matrix interferences present in the stabilization buffer and oral fluid itself pose a considerable analytical challenge. In this technical note, the SCIEX 7500 System is shown to provide the required levels of sensitivity, robustness and performance for the accurate quantification of pg/mL levels of THC-COOH in oral fluid without the need for derivatization. 

Figure 1. High sensitivity on the SCIEX 7500 System enabled trace level detection of THC-COOH in oral fluid. XICs showing the quantifier ion traces for the matrix blank and THC-COOH at the LLOQ for both the MRM (top) and MRM3 (bottom) workflows. 

Key advantages of the SCIEX Triple Quad 7500 System – QTRAP Ready for sensitive detection of THC-COOH in oral fluid

  • Hardware improvement on the SCIEX 7500 System provides significant gains in sensitivity by sampling more ions, resulting in greater quantification performance3
  • OptiFlow® Pro Ion Source with E Lens™ Technology provides improvements in ion generation while D Jet™ Ion Guide improves ion sampling, resulting in greater sensitivity
  • Simple dilute and shoot approach significantly reduces sample preparation time and negates the needs for time-consuming procedures such as solid-phase extraction (SPE), evaporation and reconstitution
  • Improved ion generation and sampling enables accurate and sensitive quantification of THC-COOH with an LLOQ of 50 pg/mL (50 fg on column) in oral fluid using the MRM workflow
  • The ion trap functionality of the SCIEX Triple Quad 7500 System – QTRAP® Ready was leveraged to improve sensitivity, selectivity and specificity of THC-COOH detection in oral fluid
  • MRM3 workflow was successfully used to eliminate background and matrix interferences at the low end of the calibration curve, improving signal-to-noise ratio and resulting in an LLOQ of THC-COOH of 10 pg/mL (10 fg on column) in oral fluid
  • Overall performance of the system resulted in excellent linearity with optimal precision, accuracy and reproducibility across the calibration range