Matrix-Tolerant Quantification of THC and THCA in Complex Cannabis Products Using In-Sample Calibration with Multiple...

Area of Science:

• Analytical Chemistry
• Forensic Science

Background:

• Quantifying THC and THCA in cannabis products is difficult due to matrix effects and concentration variability.
• Traditional LC-MS methods require matrix-matched calibration, which is often impractical.

Purpose of the Study:

• To develop a robust quantification method for THC and THCA without external calibration curves.
• To establish a practical, matrix-tolerant calibration strategy for routine cannabinoid analysis.

Main Methods:

• Developed an in-sample calibration curve (ISCC) method using multiple isotopologue reaction monitoring (MIRM).
• Utilized stable-isotope-labeled (SIL) THC calibrators (THC-D3 and THC-D9) to generate internal calibration points.
• Applied a response-correction factor and high-abundance native-analyte isotopologue transitions.

Main Results:

• Achieved a >600-fold dynamic range for THC and THCA quantification.
• Demonstrated excellent linearity (R2 > 0.999), precision (<10% RSD), and accuracy (±10%).
• Validated the method across diverse matrices including CBD oils, gummies, creams, waxes, supplements, and plant materials.

Conclusions:

• The ISCC-MIRM framework provides a practical and matrix-tolerant calibration strategy for cannabinoid analysis.
• This method enables robust quantification of THC and THCA in various consumer and forensic samples.
• Eliminates the need for external calibration curves, simplifying routine analysis.