Polarity Gradient Solvent Confinement Membrane Cartridge to Broaden Metabolite Coverage of Plasma Untargeted Analysis

Various polarity chemicals exist in complex samples, such as plasma; nontargeted comprehensive analysis naturally requires multiple polar-extracted solvents; consequently, the polarity of the solvent plays a crucial role in the extraction efficiency of analytes from complex samples. In the present study, based on the diffusion behavior and nanoconfinement effect of solvents in the nanoconfined space, the polarity gradient solvent confinement liquid-phase nanoextraction (PGSC-NLPNE) protocol aimed to perform a one-step nontargeted analysis of a wide range of metabolites in plasma was established. The continuously wide range of extracted solvent polarities on carbon nanofibers/carbon fiber (CNFs/CF) membranes was achieved using a mixture of hexane, dichloromethane, methanol, and water as nanoconfined solvents. The polarities (Log