Alkanediol–hexafluoroisopropanol amphiphilic supramolecular solvent: Fabrication, characterization, and application potential for doping control of hormones and metabolic modulators in human urine

A novel amphiphilic supramolecular solvent (SUPRAS) was developed by hexafluoroisopropanol (HFIP)-induced self-assembly of 1,2-hexanediol in an aqueous matrix. Its application potential in multiclass determination was assessed by extracting from urine 10 prohibited hormones and metabolic modulators (log P from 2.38 to 7.57) listed by the World Anti-Doping Agency (WADA). This SUPRAS is stably formed across a wide pH range (2–12) and is unaffected by salt concentrations (<10 % g mL−1 of NaCl), and it has a higher density than water. The dehydration and hydrogen bonding ability of HFIP, as well as hydrophobic interactions between alkanediols, dominates the formation of the SUPRAS. The nanostructure of the SUPRAS, composed of 1,2-hexanediol, HFIP, and a high content of water (>25 %, w/w), forms large spherical micellar aggregates (10–100 μm) that exhibit amphiphilic properties. A 1,2-hexanediol-HFIP SUPRAS-based liquid-phase microextraction (LPME) method for detection of selected prohibited drugs in urine coupled with liquid chromatography–tandem mass spectrometry (LC-MS/MS) was established, optimized, and validated. The method showed fast extraction time (30 s of vortex) and low solvent consumption (160 μL of organic solvent). Under the optimal conditions (7 % g mL−1 of 1,2-hexanediol, 10 % v/v of HFIP), the SUPRAS achieved high extraction efficiencies (>80 %) and an enrichment factor of 6.0, with minimal matrix effects for all analytes due to its high amphiphilicity and large surface area. The method demonstrated excellent linearity (R ≥ 0.9909), with method limits of detection ranging from 0.018 to 0.18 ng mL−1 and method limits of quantitation ranging from 0.060 to 0.60 ng mL−1, which are well below the minimum required performance levels set by authorities. Furthermore, the intra- and inter-day relative recoveries for spiked human urine samples varied in the ranges of 90.3 %–121 % and 88.1–119 %, respectively, with relative standard deviations less than 13 % and 19 %, respectively. This SUPRAS-based LPME method proves to be simple, highly efficient, and eco-friendly, and it has promising potential for multiclass determination in doping control.