In-tube solid-phase microextraction with a dummy molecularly imprinted monolithic capillary coupled to ultra-performance liquid chromatography-tandem mass spectrometry to determine cannabinoids in plasma samples.

A selective and sensitive method that uses automated in-tube solid-phase microextraction coupled to ultra-performance liquid chromatography-tandem mass spectrometry (in-tube SPME/UHPLC-MS/MS) was developed to determine cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) in plasma samples. A new dummy molecularly imprinted monolithic capillary (MIP monolith) for in-tube SPME was prepared by in situ polymerization in a fused silica capillary; hydrogenated cannabidiol was employed as dummy template. Fourier Transform Infrared Spectroscopy (FTIR) confirmed that the synthesis reagents were incorporated into the polymer chain. On the basis of the microscopy images (scanning electron microscopy - SEM and transmission electron microscopy - TEM), the MIP monolithic phase presented larger pores than the non-imprinted monolithic phase (NIP monolith), as well as a skeleton comprising clusters consisting of microspheres. By optimizing the polymerization conditions, the MIP monolith specifically recognized CBD and Δ9-THC. The MIP monolith had CBD and Δ9-THC sorption capacity of 148.05 and 44.49 ng cm^-3, respectively. The capillary was reused over fifty times without significant changes in its extraction efficiency. For both CBD and Δ9-THC, in-tube SPME/UHPLC-MS/MS presented linear range from 10 to 300 ng mL^-1, precision with coefficient of variation (CV) values ranging from 0.2% to 19.1% (LLOQ), and accuracy with relative standard deviation (RSD) values spanning from -9.3% to 19.6% (LLOQ). The developed method was successfully applied to determine cannabinoid levels in plasma samples from volunteer patients in treatment with CBD.