Enhanced microfluidic open interface for the direct coupling of solid phase microextraction with liquid electron ionization-tandem mass spectrometry

•New rapid transfer of the sample to liquid electron ionization (LEI)-MS/MS system.•High signal-to-noise ratio, enhanced peak shape, and fast and sensitive results.•The undemanding workflow shows a reduced environmental impact.•Fentanyl was used as a model compound without chromatographic separation. Solid-phase microextraction (SPME) directly coupled to MS is a widespread technique for determining small molecules in different matrices in many application fields. Here we present a modified microfluidic open interface (MOI) connected to a passive-flow-splitter device (PFS) for the direct coupling of SPME to a liquid-electron ionization (LEI) interface in a tandem mass spectrometer for the analysis of complex biological samples. No chromatographic separation is involved. The new MOI-PFS configuration was designed to speed up the sample transfer to MS, improving the signal-to-noise ratio and peak shape and leading to fast and sensitive results. MOI-PFS-LEI-MS/MS experiments were conducted using fentanyl as a model compound in water and blood serum. The method uses a C18 Bio-SPME fiber by direct immersion (3 min) in 300 µL of the sample followed by rapid desorption (1 min) in a flow isolated volume (MOI chamber, 2.5 µL) filled with 100% acetonitrile. The PFS permits the rapid transfer of a fraction of the sample into the MS via the LEI interface. The optimal conditions were obtained at a flow rate of 10 µL·min−1 and a 1:20 split ratio. Altogether, extraction, desorption, and analysis require approximately 5 min. Good interday and intraday precision, excellent linearity and LOQs in the µg·L−1 range were obtained for fentanyl in water and serum. Greenness evaluation demonstrated a limited environmental impact of this technique.