Proof of cannabis administration by sensitive detection of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid in hair using selective methylation and application of liquid chromatography- tandem and multistage mass spectrometry
Version of Record online: 6 NOV 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Drug Testing and Analysis
Special Issue: Cannabinoids part II: The current situation with cannabinoids
Volume 6, Issue 1-2, pages 112–118, January-February 2014
How to Cite
Thieme, D., Sachs, H. and Uhl, M. (2014), Proof of cannabis administration by sensitive detection of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid in hair using selective methylation and application of liquid chromatography- tandem and multistage mass spectrometry. Drug Test Analysis, 6: 112–118. doi: 10.1002/dta.1565
- Issue online: 14 JAN 2014
- Version of Record online: 6 NOV 2013
- Manuscript Accepted: 11 SEP 2013
- Manuscript Revised: 3 SEP 2013
- Manuscript Received: 17 MAY 2013
- forensic toxicology;
- substance abuse detection;
- liquid chromatography;
- mass spectrometry
The identification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in hair represents an exceptional forensic analytical challenge due to low target concentrations in a complex matrix. Several dedicated techniques [gas chromatography – negative chemical ionization- tandem mass spectrometry (GC-NCI-MS/MS) or GC-GC-MS couplings] were specifically introduced into forensic toxicology aiming to a selective and sensitive identification of THCCOOH in hair. The combination of liquid-chromatography (LC) and MS/MS gained an outstanding relevance in forensic toxicology (including the detection of cannabinoids). However, its application to hair matrix is characterized by a lack of specificity which is due to the unspecific decarboxylation as most abundant fragmentation reaction.
Therefore, various chemical modifications of the carboxyl and/or phenolic hydroxyl groups were examined to improve the selectivity. The selective methylation of the 9-carboxyl-group proved to be the most efficient derivatization procedure. Hair extracts were redissolved in acetonitrile and after addition of few milligrams of solid sodium carbonate derivatized with 25 μL methyl iodide. The resulting THC-9-carboxymethylester was separated by conventional reverse phase LC and selectively detected using negative electrospray ionization by recording the fragmentation reactions 357➔325 and 357➔297. Resulting limits of quantification were below 100 fg/mg. A further significant improvement was achieved by application of the multistage MS3 fragmentation 357➔325➔297. To verify the validity of this procedure, a systematic quantitative comparison of THCCOOH concentrations in hair with data from a well established GC-NCI-MS/MS technique was performed. Both techniques proved to be in good accordance (R2 =0.647, p = <0.001) and equally suitable for hair testing of THCCOOH. Copyright © 2013 John Wiley & Sons, Ltd.