###### Abstract  
Octadecyl (C\({}_{18}\)) groups are arguably the most popular ligands used for preparation of solid phase microextraction (SPME) devices. However, conventional C\({}_{18}\)-bonded silica particles are not fully compatible with the nearly 100% aqueous composition of typical biological samples (e.g., plasma, saliva, or urine). This study presents the first evaluation of thin-film SPME devices coated with special water-compatible C\({}_{18}\)-bonded particles. Device performance was assessed by extracting a mixture of 30 model compounds that exhibited various chemical structures and properties, such as hydrophobicity. Additionally, nine unique compositions of desorption solvents were tested. Thin-film SPME devices coated with C\({}_{18}\)-bonded silica particles with polar end-capping groups (10 \(\upmu\)m) were compared with conventional trimethylsilane end-capped C\({}_{18}\)-bonded silica particles of various sizes (5, 10, and 45 \(\upmu\)m) and characteristics. Polar end-capped particles provided the best extraction efficacy and were characterized by the strongest correlations between the efficacy of the extraction process and the hydrophobicity of the analytes. The results suggest that the original features of octadecyl ligands are best preserved in aqueous conditions by polar end-capped particles, unlike with conventional trimethylsilane end-capped particles that are currently used to prepare SPME devices. The benefits associated with this improved type of coating encourage further implementation of microextraction as greener alternative to the traditional sample preparation methods. s 2021 26  
fact is perhaps best highlighted by the currently available SPME devices that are designed for direct immersion into liquid samples. Such solutions are particularly sought when so-called \"green\" extraction procedures are desired or during the analysis of thermally unstable and non-volatile compounds that cannot be analysed with gas chromatography. In such cases, C\({}_{18}\)-based coatings are one of only two options that are marketed as SPME devices and are compatible with liquid chromatography; the other option is PDMS/DVB (polydimethylsiloxane/divinylbenzene). SPME is considered a \"greener\" alternative to concurrent sample preparation techniques. In accordance with the principles of Green Analytical Chemistry, microextraction methods reduce organic solvents consumption, and combine sample collection, extraction and analyte enrichment above required concentration into a single step [2; 3; 4]. Additionally, the method is characterized by low energy consumption, low laboratory waste production, and device reusability, while still enabling performance comparable or superior to the traditional methods [5]. C\({}_{18}\)-coated SPME tips and fibers are already popular around the world, as indicated by the publications of many research groups within the last 2 years [6; 7; 8; 9]. C\({}_{18}\) is also one of most popular coating types for the development of new SPME solutions, such as thin-film microextraction (TFME) blades. Although just recently commercialized, the format of TFME had already been shown to be useful in high-throughput analysis of biological fluids due to its physical stability, long-term reusability, and high degree of reproducibility [10; 11]. Additionally, TFME is characterized by a greater surface area, which increases the extraction efficacy (yield), and thin layer(s) of the coating that makes attainment of thermodynamic equilibrium of the process easier compared to commercially available SPME tips or fibers. Concurrently, the format of the blades allows extraction from common 96-well deep well plates, which enables full or partial automation of the extraction process and yields a large improvement in sample throughput [12]. TFME blades with C\({}_{18}\) coatings were first used to extract four benzodiazep from urine and phosphate-buffered saline (PBS) in 2009 [13].