Novel microsampling approach using fabric-phase sorptive extraction (FPSE) for cannabinoid analysis in blood

The most important bioactive specialised metabolites of Cannabis sp. include cannabinoids, namely tetrahydrocannabinol (THC), cannabidiol (CBD) and their analogues. They are promising compounds with many biological activities, although THC is also known as an illicit compound in several countries. Due to their widespread occurrence and biological activity, cannabinoids are frequently investigated in terms of detection and quantification in various biological matrices. The increasing introduction of products based on plant derivatives and their compounds in the recreational, industrial, pharmaceutical, and illicit markets demands the constant development and refinement of rapid and reliable methods for the determination of these analytes in biological samples. Blood microsampling has emerged as a pivotal innovation in bioanalytical science, offering minimally invasive collection, reduced solvent consumption, and broad reliability and applicability across modern workflows. In this study, an innovative dried microsampling technology based on fabric phase sorptive extraction (FPSE) has been exploited for whole blood sampling, using polymeric fabric patches coated with three different sorbent chemistries: polyethylene glycol (CW20M), polydimethylsiloxane (PDMS) and polytetrahydrofuran (PTHF), for the analysis of two main active cannabinoids and five of their metabolites. An efficient HPLC-MS/MS method was developed, obtaining r2 ≥ 0.9991, LOD ≤ 0.5 ng/mL and LOQ ≤ 1.5 ng/mL for all analytes. Just 20 µL of whole blood was needed to generate a satisfactory dried FPSE spot. The sorbent activation procedures were optimised for the different chemistries, ensuring compatibility with the analytes and high extraction efficiency. Dried sample pretreatment steps by solvent extraction were optimised before HPLC-MS/MS analysis. Analytical results were satisfactory for all analytes, with recovery always higher than 85 %, blood matrix effect lower than 14 % and FPSE matrix effect lower than 9 %. For intraday precision, the RSD value was consistently below 9.3 %, while it was lower than 9.8 % for interday precision. This is the first study where FPSE has been applied to the determination of THC, CBD and their main endogenous metabolites as a novel blood microsampling-based approach.