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A new concept of paper-based device has been developed combining the advantages of cellulose supports and the rich surface chemistry of metal-organic frameworks (MOFs). The composite, named as NH2-UiO-66@paper, has been developed for the isolation of synthetic cannabinoid receptor agonists (SCRAs) in oral fluids, trying to mimic the interactions of those compounds with the human CB1R and CB2R receptors, mainly governed by hydrogen bonding and π-interactions with serine and histidine residues. MOF selection (UiO-66) and functionalization of the ligand (2-aminoterephthalic acid) has been done according to the following criteria: (i) water stability of the selected MOF, and (ii) promoting appropriate interactions with SCRAs due to the MOF nature. NH2-UiO-66@paper composite has been characterized in depth and the results confirmed that the material is stable at the temperature selected for thermal desorption (230 °C). Furthermore, the developed method provided appropriate precision values (RSD < 12%) and a limit of detection as low as 10 ng using ion mobility spectrometry as analytical technique. Lastly, the method has been successfully applied to the isolation of several synthetic cannabinoids from oral fluids. This method claims to be an interesting approach for expanding the combination of MOFs with sustainable support and represents a promising alternative to sophisticated and non-portable systems due to the negligible sample treatment required and the simplicity of the operation, which can be applied with screening purposes. [ABSTRACT FROM AUTHOR]