Analytical and Bioanalytical Chemistry

, Volume 409, Issue 5, pp 1207–1220 | Cite as

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

  • Juan Sánchez-González
  • Rocío Salgueiro-Fernández
  • Pamela Cabarcos
  • Ana María Bermejo
  • Pilar Bermejo-Barrera
  • Antonio Moreda-PiñeiroEmail author
Research Paper


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.

Graphical Abstract


Molecularly imprinted polymer Microsolid-phase extraction Plasma Urine Cannabinoids High performance liquid chromatography–tandem mass spectrometry 



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.

Compliance with ethical standards

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.

Supplementary material

216_2016_46_MOESM1_ESM.pdf (805 kb)
ESM 1 (PDF 805 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Juan Sánchez-González
    • 1
  • Rocío Salgueiro-Fernández
    • 1
  • Pamela Cabarcos
    • 2
  • Ana María Bermejo
    • 2
  • Pilar Bermejo-Barrera
    • 1
  • Antonio Moreda-Piñeiro
    • 1
    Email author
  1. 1.Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of ChemistryUniversidade de Santiago de CompostelaSantiago de CompostelaSpain
  2. 2.Department of Pathologic Anatomy and Forensic Sciences, Faculty of MedicineUniversidade de Santiago de CompostelaSantiago de CompostelaSpain

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