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Isotope-Coded Derivatization Enables Accurate LC-MS/MS Quantification of Urinary THC-COOH without Isotope-Labeled
Maiko Kusano1, Shimba Kawasue2, Yu-Ki Sakamoto3
1Department of Legal Medicine, Showa Medical University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
Journal of the American Society for Mass Spectrometry
|June 24, 2026
Summary
This study introduces an isotope-coded derivatization method for quantifying cannabis metabolite THC-COOH in urine. This approach avoids costly isotope-labeled standards, making forensic toxicology analysis more accessible and reliable.
Area of Science:
- Forensic Toxicology
- Analytical Chemistry
- Mass Spectrometry
Background:
- Quantitative determination of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in urine is crucial for verifying cannabis use.
- Current LC-MS/MS methods rely on expensive and regulated isotope-labeled standards, limiting accessibility.
Purpose of the Study:
- To develop an isotope-coded derivatization (ICD) strategy for quantifying urinary THC-COOH.
- To enable isotope-dilution-equivalent quantification without commercial isotope-labeled cannabinoid standards.
Main Methods:
- THC-COOH was derivatized using isopropyl-piperidine carboxylic acid hydrazide (IPPAH) and its deuterated analogue (IPPAH-d6).
- Parallel derivatization created a chemically matched analyte/internal standard pair for LC-MS/MS analysis.
- Analyzed derivatives for linearity, accuracy, precision, and matrix effect compensation.
Main Results:
- Derivatives showed stable coelution and matched ionization behavior.
- Quantitative analysis demonstrated excellent linearity (r2 > 0.999) from 1-500 ng/mL.
- Accuracy ranged from 81.8-108.6% with precision below 10%; matrix effects were effectively compensated (97-109%).
- Derivatized samples were stable for at least 72 hours.
Conclusions:
- The ICD strategy provides a reliable alternative to conventional isotope dilution for urinary THC-COOH quantification.
- This method eliminates the need for expensive isotope-labeled cannabinoid standards, enhancing accessibility.
- The approach simplifies sample preparation and broadens the potential of isotope-coded derivatization in forensic mass spectrometry.
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