Skip to main content
SpringerLink
Log in

Cannabinoids assessment in plasma and urine by high performance liquid chromatography–tandem mass spectrometry after molecularly imprinted polymer microsolid-phase extraction

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

A molecularly imprinted polymer (MIP) selective for cannabinoids [Δ9-tetrahydrocannabinol (Δ9-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THC-COOH), and 11-hydroxy-Δ9-tetrahydrocannabinol (Δ9-THC-OH)] has been synthesized, fully characterized, and applied to the assessment of plasma and urine analysis of marijuana abuse by high performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). Δ9-THC-COOH was used as a template molecule, whereas ethylene glycol dimethacrylate (EGDMA) was used as a functional monomer, divinylbenzene (DVB) as a cross-linker, and 2,2′-azobisisobutyronitrile (AIBN) as an initiator. The prepared MIP was found to be highly selective for cannabinoids typically found in blood and urine, and also for cannabinol (CBN) and cannabidiol (CBD). MIP beads (50 mg) were loaded inside a cone-shaped device made of a polypropylene (PP) membrane for microsolid-phase extraction (μ-SPE) in batch mode. Optimum retention of analytes (0.1 to 1.0 mL of plasma/urine) was achieved by fixing plasma/urine pH at 6.5 and assisting the procedure by mechanical shaking (150 rpm, 40 °C, 12 min). Optimum elution conditions implied 2 mL of a 90:10 methanol/acetic acid and ultrasound extraction (35 kHz, 325 W) for 6 min. Good precision was assessed by intra-day and inter-day assays. In addition, the method was found to be accurate after intra-day and inter-day analytical recovery assays and after analyzing control serum and urine control samples. The limits of quantification were in the range of 0.36–0.49 ng L−1 (plasma analysis) and 0.47–0.57 ng L−1 (urine analysis). These values are low enough for confirmative conclusions regarding marijuana abuse through blood and urine analysis.

ᅟ

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. European Monitoring Centre for Drug and Drug Addiction. European Drug Report—trends and developments 2015. Available at: http://www.emcdda.europa.eu/attachements.cfm/att_239505_EN_TDAT15001ENN.pdf. Accessed March 30th 2016.

  2. Teixeira H, Verstraete A, Proenc P¸ Corte-Real F, Monsanto P, Vieira DN. Validated method for the simultaneous determination of Δ9-THC and Δ9-THC-COOH in oral fluid, urine and whole blood using solid-phase extraction and liquid chromatography–mass spectrometry with electrospray ionization. Forensic Sci Int. 2007;170:148–55.

    Article  CAS  Google Scholar 

  3. Raharjo TJ, Verpoorte R. Methods for the analysis of cannabinoids in biological materials: a review. Phytochem Anal. 2004;15:79–94.

    Article  CAS  Google Scholar 

  4. König S, Aebi B, Lanz S, Gasser M, Weinmann W. On-line SPE LC-MS/MS for the quantification of Δ9-tetrahydrocannabinol (THC) and its two major metabolites in human peripheral blood by liquid chromatography tandem mass spectrometry. Anal Bioanal Chem. 2011;400:9–16.

    Article  Google Scholar 

  5. Sadler Simões S, Castañera Ajenjo A, Dias MJ. Qualitative and quantitative analysis of THC, 11-hydroxy-THC and 11-nor-9-carboxy-THC in whole blood by ultra-performance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom. 2011;25:2603–10.

    Article  Google Scholar 

  6. Fabritius M, Chtioui H, Battistella G, Annoni J-M, Dao K, Favrat B, et al. Comparison of cannabinoid concentrations in oral fluid and whole blood between occasional and regular cannabis smokers prior to and after smoking a cannabis joint. Anal Bioanal Chem. 2013;405:9791–803.

    Article  CAS  Google Scholar 

  7. Ferreirós N, Labocha S, Walter C, Lötsch J, Geisslinger G. Simultaneous and sensitive LC–MS/MS determination of tetrahydrocannabinol and metabolites in human plasma. Anal Bioanal Chem. 2013;405:1399–406.

    Article  Google Scholar 

  8. Sergi M, Battista N, Montesano C, Curini R, Maccarrone M, Compagnone D. Determination of the two major endocannabinoids in human plasma by μ-SPE followed by HPLC-MS/MS. Anal Bioanal Chem. 2013;405:785–93.

    Article  CAS  Google Scholar 

  9. Mercolini L, Mandrioli R, Sorella V, Somaini L, Giocondi D, Serpelloni G, et al. Dried blood spots: liquid chromatography–mass spectrometry analysis of _9-tetrahydrocannabinol and its main metabolites. J Chromatogr A. 2013;1271:33–40.

    Article  CAS  Google Scholar 

  10. Hidvégi E, Somogyi GP. Determination of main tetrahydrocannabinoids by GC-MS: impact of protein precipitation by acetonitrile on solid phase extraction of cannabinoids from human serum. Pharmazie. 2014;69:417–9.

    Google Scholar 

  11. Toennes SW, Hanisch S, Pogoda W, Wunder C, Paulke A. Pitfall in cannabinoid analysis—detection of a previously unrecognized interfering compound in human serum. Anal Bioanal Chem. 2015;407:463–70.

    Article  CAS  Google Scholar 

  12. Basheer C, Alnedhary AA, Madhava Rao BS, Valliyaveettil S, Lee HK. Development and application of porous membrane-protected carbon nanotube micro-solid-phase extraction combined with gas chromatography/mass spectrometry. Anal Chem. 2006;78:2853–8.

    Article  CAS  Google Scholar 

  13. Basheer C, Chong HG, Hii TM, Lee HK. Application of porous membrane-protected micro-solid-phase extraction combined with HPLC for the analysis of acidic drugs in waste water. Anal Chem. 2007;79:6845–50.

    Article  CAS  Google Scholar 

  14. Basheer C, Alnedhary AA, Madhava Rao BS, Lee HK. Determination of carbamate pesticides using micro-solid-phase extraction combined with high-performance liquid chromatography. J Chromatogr A. 2009;1216:211–6.

    Article  CAS  Google Scholar 

  15. Khayoon WS, Saad B, Salleh B, Manaf NHA, Latiff AA. Micro-solid phase extraction with liquid chromatography–tandem mass spectrometry for the determination of aflatoxins in coffee and malt beverage. Food Chem. 2014;147:287–94.

    Article  CAS  Google Scholar 

  16. Kanimozhi S, Basheer C, Narasimhan K, Liu L, Koh S, Xue F, et al. Application of porous membrane protected micro-solid-phase-extraction combined with gas chromatography–mass spectrometry for the determination of estrogens in ovarian cyst fluid samples. Anal Chim Acta. 2011;687:56–60.

    Article  CAS  Google Scholar 

  17. Nsubuga H, Basheer C. Determination of haloacetic acids in swimming pool waters by membrane-protected micro-solid phase extraction. J Chromatogr A. 2013;1315:47–52.

    Article  CAS  Google Scholar 

  18. Lim TH, Hu L, Yang C, He C, Lee HK. Membrane assisted micro-solid phase extraction of pharmaceuticals with amino and urea-grafted silica gel. J Chromatogr A. 2013;1316:8–14.

    Article  CAS  Google Scholar 

  19. Ge D, Lee HK. Water stability of zeolite imidazolate framework 8 and application to porous membrane-protected micro-solid-phase extraction of polycyclic aromatic hydrocarbons from environmental water samples. J Chromatogr A. 2011;1218:8490–5.

    Article  CAS  Google Scholar 

  20. Ge D, Lee HK. Sonication-assisted emulsification microextraction combined with vortex-assisted porous membrane-protected micro-solid-phase extraction using mixed zeolitic imidazolate frameworks 8 as sorbent. J Chromatogr A. 2012;1263:1–6.

    Article  CAS  Google Scholar 

  21. Ge D, Lee HK. Zeolite imidazolate frameworks 8 as sorbent and its application to sonication-assisted emulsification microextraction combined with vortex-assisted porous membrane-protected micro-solid-phase extraction for fast analysis of acidic drugs in environmental water samples. J Chromatogr A. 2012;1257:19–24.

    Article  CAS  Google Scholar 

  22. Ara KM, Pandidan S, Aliakbari A, Raofie F, Amini M. Porous-membrane-protected polyaniline-coated SBA-15 nanocomposite micro-solid-phase extraction followed by high-performance liquid chromatography for the determination of parabens in cosmetic products and wastewater. J Sep Sci. 2015;38:1213–24.

    Article  CAS  Google Scholar 

  23. Wang T, Wang J, Zhang C, Yang Z, Dai X, Cheng M, et al. Metal-organic framework MIL-101(Cr) as a sorbent of porous membrane-protected micro-solid-phase extraction for the analysis of six phthalate esters from drinking water: a combination of experimental and computational study. Analyst. 2015;140:5308–16.

    Article  CAS  Google Scholar 

  24. Chen L, Xu S, Li J. Recent advances in molecular imprinting technology: current status, challenges and highlighted applications. Chem Soc Rev. 2011;40:2922–42.

    Article  CAS  Google Scholar 

  25. Martín-Esteban A. Molecularly-imprinted polymers as a versatile, highly selective tool in sample preparation. Trends Anal Chem. 2013;45:169–81.

    Article  Google Scholar 

  26. Chen L, Wang X, Lu W, Wu X, Lia J. Molecular imprinting: perspectives and applications. Chem Soc Rev. 2016;45:2137–211.

    Article  CAS  Google Scholar 

  27. Tan F, Deng M, Liu X, Zhao H, Li X, Quan X, et al. Evaluation of a novel microextraction technique for aqueous samples: porous membrane envelope filled with multiwalled carbon nanotubes coated with molecularly imprinted polymer. J Sep Sci. 2011;34:707–15.

    Article  CAS  Google Scholar 

  28. Lee TP, Saad B, Khayoon WS, Salleh B. Molecularly imprinted polymer as sorbent in micro-solid phase extraction of ochratoxin A in coffee, grape juice and urine. Talanta. 2012;88:129–35.

    Article  CAS  Google Scholar 

  29. Yin X-Y, Luo Y-M, Fu J, Zhong Y-Q, Liu Q-S. Determination of hyperoside and isoquercitrin in rat plasma by membrane protected micro-solid-phase extraction with high-performance liquid chromatography. J Sep Sci. 2012;35:384–91.

    Article  CAS  Google Scholar 

  30. Sánchez-González J, Tabernero MJ, Bermejo AM, Bermejo-Barrera P, Moreda-Piñeiro A. Porous membrane-protected molecularly imprinted polymer microsolid-phase extraction for analysis of urinary cocaine and its metabolites using liquid chromatography-tandem mass spectrometry. Anal Chim Acta. 2015;898:50–9.

    Article  Google Scholar 

  31. Sánchez-González J, García-Carballal S, Cabarcos P, Tabernero MJ, Bermejo-Barrera P, Moreda-Piñeiro A. Determination of cocaine and its metabolites in plasma by porous membrane-protected molecularly imprinted polymer micro-solid-phase extraction and liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2016;1451:15–22.

    Article  Google Scholar 

  32. Cela-Pérez MC, Bates F, Jiménez-Morigosa C, Lendoiro E, de Castro A, Cruz A, et al. Water-compatible imprinted pills for sensitive determination of cannabinoids in urine and oral fluid. J Chromatogr A. 2016;1429:53–64.

    Article  Google Scholar 

  33. Sánchez-González J, Tabernero MJ, Bermejo AM, Bermejo-Barrera P, Moreda-Piñeiro A. Development of magnetic molecularly imprinted polymers for solid phase extraction of cocaine and metabolites in urine before high performance liquid chromatography–tandem mass spectrometry. Talanta. 2016;147:641–9.

    Article  Google Scholar 

  34. Sánchez-González J, Barreiro-Grille T, Cabarcos P, Tabernero MJ, Bermejo-Barrera P, Moreda-Piñeiro A. Magnetic molecularly imprinted polymer based–micro-solid phase extraction of cocaine and metabolites in plasma followed by high performance liquid chromatography–tandem mass spectrometry. Microchem J. 2016;127:206–12.

    Article  Google Scholar 

  35. Chantada-Vázquez MP, Sánchez-González J, Peña-Vázquez E, Tabernero MJ, Bermejo AM, Bermejo-Barrera P, et al. Synthesis and characterization of novel molecularly imprinted polymer-coated Mn-doped ZnS quantum dots for specific fluorescent recognition of cocaine. Biosens Bioelectron. 2016;75:213–21.

    Article  Google Scholar 

  36. Chantada-Vázquez MP, Sánchez-González J, Peña-Vázquez E, Tabernero MJ, Bermejo AM, Bermejo-Barrera P, et al. Simple and sensitive molecularly imprinted polymer-Mn-doped ZnS quantum dots based fluorescence probe for cocaine and metabolites determination in urine. Anal Chem. 2016;88:2734–41.

    Article  Google Scholar 

  37. Wu X, Wang X, Lu W, Wang X, Li J, You H, et al. Water-compatible temperature and magnetic dual-responsive molecularly imprinted polymers for recognition and extraction of bisphenol A. J Chromatogr A. 2016;435:30–8.

    Article  Google Scholar 

  38. Moreda-Piñeiro A, Moreda-Piñeiro J, Bermejo-Barrera P. Sample pre-treatment methods for organometallic species determination. In: Bakirdere S, editor. Speciation studies in soil, sediment and environmental samples. Boca Raton: CRC Press Taylor & Francis Group; 2014. p. 19–201.

    Google Scholar 

  39. Basheer C, Jayaraman A, Kee MK, Valiyaveettil S, Lee HK. Polymer-coated hollow-fiber microextraction of estrogens in water samples with analysis by gas chromatography–mass spectrometry. J Chromatogr A. 2005;1100:137–43.

    Article  CAS  Google Scholar 

  40. Basheer C, Lee J, Pedersen-Bjergaard S, Rasmussen KE, Lee HK. Simultaneous extraction of acidic and basic drugs at neutral sample pH: a novel electro-mediated microextraction approach. J Chromatogr A. 2010;1217:6661–7.

    Article  CAS  Google Scholar 

  41. Vindenes V, Lund HME, Andresen W, Gjerde H, Ikdahl SE, Christophersen AS, et al. Detection of drugs of abuse in simultaneously collected oral fluid, urine and blood from Norwegian drug drivers. Forensic Sci Int. 2012;219:165–71.

    Article  CAS  Google Scholar 

  42. Horwitz W. Evaluation of analytical methods used for regulation of foods and drugs. Anal Chem. 1982;54:67A–76A.

    Article  CAS  Google Scholar 

  43. Baselt RC. Disposition of toxic drugs and chemicals in man. 9th edition. Seal Beach: Biomedical Publications; 2011. p. 1644–8.

    Google Scholar 

Download references

Acknowledgments

The authors wish to thank the Dirección Xeral de I+D – Xunta de Galicia (Project number 10CSA209042PR) and the European Regional Development Funds 2007-2013 (FEDER), Infrastructure Program UNST-10-1E-1195 (Ministerio de Economía y Competitividad, Spain) for financial support.

Author information

Authors and Affiliations

  1. Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of Chemistry, Universidade de Santiago de Compostela, Avenida das Ciencias s/n, 15782, Santiago de Compostela, Spain

    Juan Sánchez-González, Rocío Salgueiro-Fernández, Pilar Bermejo-Barrera & Antonio Moreda-Piñeiro

  2. Department of Pathologic Anatomy and Forensic Sciences, Faculty of Medicine, Universidade de Santiago de Compostela, Rúa de San Francisco s/n, 15782, Santiago de Compostela, Spain

    Pamela Cabarcos & Ana María Bermejo

Authors
  1. Juan Sánchez-González
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rocío Salgueiro-Fernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pamela Cabarcos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ana María Bermejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pilar Bermejo-Barrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Moreda-Piñeiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Moreda-Piñeiro.

Ethics declarations

The authors declare that the studies have been approved by the Comité Ético de Investigación Clínica de Galicia (registration code CEIC de Galicia 2010/372).

The approved document by the CEIC de Galicia requires an informed consent from all volunteers who participated in the study. The authors declare therefore that all volunteers have signed an informed consent for allowing the use of the provided blood and urine samples in this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 805 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sánchez-González, J., Salgueiro-Fernández, R., Cabarcos, P. et al. Cannabinoids assessment in plasma and urine by high performance liquid chromatography–tandem mass spectrometry after molecularly imprinted polymer microsolid-phase extraction. Anal Bioanal Chem 409, 1207–1220 (2017). https://doi.org/10.1007/s00216-016-0046-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-016-0046-3

Keywords

Search

Navigation