Advertisement

Analytical and Bioanalytical Chemistry

, Volume 406, Issue 15, pp 3589–3597 | Cite as

Molecularly imprinted polymer for selective determination of Δ9-tetrahydrocannabinol and 11-nor-Δ9-tetrahydrocannabinol carboxylic acid using LC-MS/MS in urine and oral fluid

  • E. LendoiroEmail author
  • A. de Castro
  • H. Fernández-Vega
  • M. C. Cela-Pérez
  • J. M. López-Vilariño
  • M. V. González-Rodríguez
  • A. Cruz
  • M. López-Rivadulla
Research Paper
  • 601 Downloads
Part of the following topical collections:
  1. Forensic Toxicology

Abstract

The use of molecularly imprinted polymers (MIPs) for solid phase extraction (MISPE) allows a rapid and selective extraction compared with traditional methods. Determination of Δ9-tetrahydrocannabinol (THC) and 11-nor-Δ9-tetrahydrocannabinol carboxylic acid (THC-COOH) in oral fluid (OF) and urine was performed using homemade MISPEs for sample clean-up and liquid chromatography tandem mass spectrometry (LC-MS/MS). Cylindrical MISPE shaped pills were synthesized using catechin as a mimic template. MISPEs were added to 0.5 mL OF or urine sample and sonicated 30 min for adsorption of analytes. For desorption, the MISPE was transfered to a clean tube, and sonicated for 15 min with 2 mL acetone:acetonitrile (3:1, v/v). The elution solvent was evaporated and reconstituted in mobile phase. Chromatographic separation was performed using a SunFire C18 (2.5 μm; 2.1 × 20 mm) column, and formic acid 0.1 % and acetonitrile as mobile phase, with a total run time of 5 min. The method was fully validated including selectivity (no endogenous or exogenous interferences), linearity (1–500 ng/mL in OF, and 2.5–500 ng/mL in urine), limit of detection (0.75 and 1 ng/mL in OF and urine, respectively), imprecision (%CV <12.3 %), accuracy (98.2–107.0 % of target), extraction recovery (15.9–53.5 %), process efficiency (10.1–46.2 %), and matrix effect (<−55 %). Analytes were stable for 72 h in the autosampler. Dilution 1:10 was assured in OF, and Quantisal™ matrix effect showed ion suppression (<−80.4 %). The method was applied to the analysis of 20 OF and 11 urine specimens. This is the first method for determination of THC and THC-COOH in OF using MISPE technology.

Keywords

Molecularly imprinted polymer Oral fluid Urine THC THC-COOH LC-MS/MS 

Notes

Acknowledgments

E. Lendoiro would like to thank Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, for her predoctoral contract (PRE/2011/072), and A. de Castro thanks Ministerio de Ciencia e Innovación, Gobierno de España, for her “Torres Quevedo” contract (PTQ-10-03936).

References

  1. 1.
    Sellergren B (2000) Molecularly imprinted polymers. Man-made mimics of antibodies and their application in analytical chemistry. Elsevier, UKGoogle Scholar
  2. 2.
    Komiyama M, Takeuchi T, Mukawa T, Asanuma H (2003) Molecular imprinting: from fundamental to applications. Wiley-VCH, WeinheimGoogle Scholar
  3. 3.
    Martín-Esteban A (2013) Molecularly-imprinted polymers as a versatile, highly selective tool in sample preparation. Trends Anal Chem 45:169–181CrossRefGoogle Scholar
  4. 4.
    Caro E, Marcé RM, Borrull F, Cormack PAG, Sherrington DC (2006) Application of molecularly imprinted polymers to solid-phase extraction of compounds from environmental and biological samples. Trends Anal Chem 25(2):143–154CrossRefGoogle Scholar
  5. 5.
    Castro-López MM, Cela-Pérez MC, Dopico-García MS, López-Vilariño JM, González-Rodríguez MV, Barral-Losada LF (2012) Preparation, evaluation and characterization of quercetin-molecularly imprinted polymer for preconcentration and clean-up of catechins. Anal Chim Acta 721:68–78CrossRefGoogle Scholar
  6. 6.
    Whitcombe MJ, Alexander C, Vulfson EN (1997) Smart polymers for the food industry. Trends Food Sci Technol 8(5):140–145CrossRefGoogle Scholar
  7. 7.
    Yu Y, Ye L, Haupt K, Mosbach K (2002) Formation of a class of enzyme inhibitors (drugs), including a chiral compound, by using imprinted polymers or biomolecules as molecular-scale reaction vessels. Angew Chem 41:4640–4463Google Scholar
  8. 8.
    Sellergren B, Allender CJ (2005) Molecularly imprinted polymers: A bridge to advanced drug delivery. Adv Drug Deliv Rev 57(12):1733–1741CrossRefGoogle Scholar
  9. 9.
    Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings (2012) Substance Abuse and Mental Health Services Administration, Rockville. http://www.samhsa.gov/data/NSDUH/2012SummNatFindDetTables/NationalFindings/NSDUHresults2012.htm. Accessed 22 Oct 2013
  10. 10.
    Annual report on the state of the drugs problem in Europe (2012) European Monitoring Centre for Drugs and Drug Addiction, Lisbon. http://www.emcdda.europa.eu/publications/annual-report/2012. Accessed 22 Oct 2013
  11. 11.
    Nestic M, Babic S, Pavlovic DM, Sutlovic D (2013) Molecularly imprinted solid phase extraction for simultaneous determination of ∆9-tetrahydrocannabinol and its main metabolites by gas chromatography–mass spectrometry in urine samples. Forensic Sci Int 231:317–324CrossRefGoogle Scholar
  12. 12.
    Cela-Pérez MC, Castro-López MM, Lasagabáster-Latorre A, López-Vilariño JM, González-Rodríguez MV, Barral-Losada LF (2011) Synthesis and characterization of bisphenol-A imprinted polymer as a selective recognition receptor. Anal Chim Acta 706(2):275–284CrossRefGoogle Scholar
  13. 13.
    European Union Decision 2002/657/EC (17/8/2002) (2002) Off. J. Eur. Commun. 221:8-36Google Scholar
  14. 14.
    Krouwer JS, Rabinowitz R (1984) How to improve estimates of imprecision. Clin Chem 30:290–292Google Scholar
  15. 15.
    Concheiro M, de Castro A, Quintela O, Cruz A, López-Rivadulla M (2008) Determination of illicit and medicinal drugs and their metabolites in oral fluid and preserved oral fluid by liquid chromatography-tandem mass spectrometry. Anal and Bioanal Chem 391(6):2329–2338CrossRefGoogle Scholar
  16. 16.
    US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (2001) Guidance for industry: Bioanalytical method validation, Rockville, MD. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070107.pdf. Accessed 22 Oct 2013
  17. 17.
    Standard practices for method validation in forensic toxicology (2013) Scientific working group for forensic toxicology (SWGTOX) http://www.swgtox.org/. Accesed 22 Oct 2013
  18. 18.
    Quintela O, Andrenyak DM, Hoggan AM, Crouch DJ (2007) A validated method for the detection of ∆9-tetrahydrocannabinol and 11-nor-9-carboxy-∆9-tetrahydrocannabinol in oral fluid samples by liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. J Anal Toxicol 31(3):157–164CrossRefGoogle Scholar
  19. 19.
    Goodwin RS, Darwin WD, Chiang CN, Shih M, Li S-H, Huestis MA (2008) Urinary elimination of 11-nor-9-carboxy-∆9-tetrahydrocannabinol in cannabis users during continuously monitored abstinence. J Anal Toxicol 32(8):562–569CrossRefGoogle Scholar
  20. 20.
    Frazee CC 3rd, Kiscoan M, Garg U (2010) Quantification of total 11-nor-9-carboxy-∆9-tetrahydrocannabinol in urine and blood using gas chromatography–mass spectrometry (GC-MS). Methods Mol Biol 603:137–144CrossRefGoogle Scholar
  21. 21.
    Moffat AC, Osselton MD, Widdop B, Watts J (2011) Clarke’s analysis of drugs and poisons, volume 2. Pharmaceutical, LondonGoogle Scholar
  22. 22.
    Coulter C, Garnier M, Moore C (2012) Analysis of Tetrahydrocannabinol and its metabolite, 11-nor-Δ9- tetrahydrocannabinol-9-carboxylic acid, in oral fluid using liquid chromatography with tandem mass spectrometry. J Anal Toxicol 36:413–417CrossRefGoogle Scholar
  23. 23.
    Concheiro M, Lee D, Lendoiro E, Huestis MA (2013) Simultaneous quantification of Δ(9)-tetrahydrocannabinol, 11-nor-9-carboxy-tetrahydrocannabinol, cannabidiol and cannabinol in oral fluid by microflow-liquid chromatography-high resolution mass spectrometry. J Chromatogr A 1297:123–130CrossRefGoogle Scholar
  24. 24.
    Milman G, Barnes AJ, Lowe RH, Huestis MA (2010) Simultaneous quantification of cannabinoids and metabolites in oral fluid by two-dimensional gas chromatography mass spectrometry. J Chromatogr A 1217:1513–1521CrossRefGoogle Scholar
  25. 25.
    Lee D, Milman G, Barnes AJ, Goodwin RS, Hirvonen J, Huestis MA (2011) Oral fluid cannabinoids in chronic, daily cannabis smokers during sustained, monitored abstinence. Clin Chem 57:1127–1136CrossRefGoogle Scholar
  26. 26.
    Walsh JM, Verstraete AG, Huestis MA, Morland J (2008) Guidelines for research on drugged driving. Addiction 103(8):1258–1268CrossRefGoogle Scholar
  27. 27.
    Houwing S, Hagenzieker M, Mathijssen R, Bernhoft IM, Hels T, Janstrup K, van der Linden T, Legrand SA, Verstraete A (2011) Prevalence of alcohol and other psychoactive substances in drivers in general traffic. Part II: Country reports. Deliverable 2.2.3. Available at: www.druid-project.eu. Accessed 17 Dic 2013

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • E. Lendoiro
    • 1
    Email author
  • A. de Castro
    • 1
    • 2
  • H. Fernández-Vega
    • 1
  • M. C. Cela-Pérez
    • 3
  • J. M. López-Vilariño
    • 3
  • M. V. González-Rodríguez
    • 3
  • A. Cruz
    • 1
  • M. López-Rivadulla
    • 1
  1. 1.Servicio de Toxicología, Instituto de Ciencias ForensesUniversidad de Santiago de CompostelaSantiago de CompostelaSpain
  2. 2.Departamento de I + DCienytechSantiago de CompostelaSpain
  3. 3.Grupo de Polímeros, Centro de Investigaciones TecnológicasUniversidad de A CoruñaFerrolSpain

Personalised recommendations