Methods and systems for delivering liquid sample to an ion source and subsequent analysis by mass spectrometry. In accordance with various aspects of the present teachings, MS-based systems and methods are provided in which desorption solvent is used in sampling interface to desorb analyte species from an SPME device that is coupled to an ion source to ionize analyte species desorbed into the desorption solvent for MS analysis (e.g., without a liquid chromatography (LC) column between the sampling interface and the ion source). In various aspects of the methods and systems described herein, configuring the sampling interface can be optimized so as to reduce the fluid volume dead space about the fluid inlet so as to concentrate the one or more analyte species desorbed at optimized conditions from the SPME substrate in a decreased volume of the desorption solvent when the SPME device is inserted into sampling interface.