Ultra-Sensitive Measurements of 11-Nor-Δ9-Tetrahydrocannabinol-9-Carboxylic Acid in Oral Fluid by Microflow Liquid Chromatography–Tandem Mass Spectrometry Using a Benchtop Quadrupole/Orbitrap Mass Spectrometer
Abstract
Oral fluid has been gaining more acceptance as the alternative matrix for forensic toxicology. Currently, Δ(9)-tetrahydrocannabinol (THC) is used as the primary target for detecting cannabis use in oral fluid. Meanwhile, THC carboxylic acid (THCA) in oral fluid is reported as a more reliable marker for cannabis abuse as its presence does not come from passive exposure. An analytical method for simultaneous quantitation of THC and THCA will be efficient for toxicology laboratories. THCA quantitation is challenging due to its very low concentration in oral fluid. Recently reported liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based methods achieved sufficient sensitivity but involved complex sample preparation procedures. We aimed to develop a sensitive LC-MS/MS method for simultaneous quantitation of THC and THCA in oral fluid with low-flow liquid chromatography and a Q Exactive mass spectrometer, using offline sample preparation of oral fluid followed by microflow LC with online sample cleanup. The total runtime of the method was 12.5 min. The method had a lower limit of quantitation of 7.5 pg/mL and was linear from 7.5 to 300 pg/mL for THCA. The intra- and interbatch precision of the method ranged from 3.3% to 9.3% for THC and THCA.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Recent advances have produced more efficient time-of-flight and single-stage Orbitrap instruments with improved linearity, resolution, and mass accuracy, which are critically important for food metabolome analysis.
“Rapid advances in technology have led to a new generation of much more efficient time-of-flight and single-stage Orbitrap (Exactive; Thermo Scientific) instruments, offering improved linearity, resolution, and mass accuracy, which will be critically important for the analysis of the food metabolome (115).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [115]
Cites
Matuszewski, B. K., Constanzer, M. L., & Chavez-Eng, C. M. (2003) · Analytical Chemistry · doi:10.1021/ac020361s · Cited by 5,348 · see citing works
Huestis, M. A., & Cone, E. J. (2004) · Journal of Analytical Toxicology · doi:10.1093/jat/28.6.394 · Cited by 208 · see citing works
Thomas, A., Geyer, H., Schänzer, W., et al. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-011-5655-2 · Cited by 159 · see citing works
Multiclass analysis of illicit drugs in plasma and oral fluids by LC-MS/MS
Sergi, M., Bafile, E., Compagnone, D., Curini, R., D'Ascenzo, G., & Romolo, F. S. (2008) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-008-2456-3 · Cited by 92 · see citing works
Moore, C. M., Coulter, C., Rana, S., Vincent, M., & Snares, J. (2006) · Journal of Analytical Toxicology · doi:10.1093/jat/30.7.409 · Cited by 55 · see citing works
Detection of THCA in Oral Fluid by GC-MS-MS
Day, D., Kuntz, D. J., Feldman, M., & Presley, L. C. (2006) · Journal of Analytical Toxicology · doi:10.1093/jat/30.9.645 · Cited by 55 · see citing works
Quintela, O., Andrenyak, D. M., Hoggan, A. M., & Crouch, D. J. (2007) · Journal of Analytical Toxicology · doi:10.1093/jat/31.3.157 · Cited by 47 · see citing works
Coulter, C., Garnier, M., & Moore, C. M. (2012) · Journal of Analytical Toxicology · doi:10.1093/jat/bks039 · Cited by 44 · see citing works
Lee, P. D., Chang, Y.-J., Chang, Y.-J., et al. (2011) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-011-5439-8 · Cited by 33 · see citing works
Tuyay, J., Coulter, C., Rodrigues, W. C., & Moore, C. M. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1324 · Cited by 31 · see citing works
Bylda, C., Leinenbach, A., Thiele, R., et al. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1334 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The food metabolome: a window over dietary exposure
Scalbert, A., Brennan, L., Manach, C., Andres-Lacueva, C., Dragsted, L. O., Draper, J., Rappaport, S. M., van der Hooft, J. J., & Wishart, D. S. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.076133 · Cited by 519 · see citing works
Oral fluid drug testing: analytical approaches, issues and interpretation of results
Desrosiers, N. A., & Huestis, M. A. (2019) · Journal of Analytical Toxicology · doi:10.1093/jat/bkz048 · Cited by 123 · see citing works
- Authors
- He, X., Kozak, M., & Nimkar, S.
- Affiliations
- ThermoFisher Scientific, 355 River Oaks Parkway, San Jose, California 95134, United States
- Corresponding author
- He, Xiang
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-08-27
- Volume
- 84
- Issue
- 18
- Pages
- 7643-7647
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W2319291470
- Cited by
- 36
- References
- 11
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 3 · 2019: 3 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 9 · 2013: 9
- FWCI
- 9.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical chemistry methods development
- Keywords
- oral fluid, forensic toxicology, tandem mass spectrometry, simultaneous quantitation
- MeSH terms
- Adult, Chromatography, High Pressure Liquid, Female, Humans, Male, Middle Aged, Saliva, Dronabinol, Tandem Mass Spectrometry
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
