The metabolomics analysis of complex samples requires the use of high resolution comprehensive separation techniques. Liquid-liquid chromatography mass spectrometry (LCxLC-MS) is such a technique. Due to solvent incompatibilities, dilution and peak dispersion effects between the first and second separation dimension, peak resolving power is lost and ion-suppression is induced. A novel LCxLC interface based on evaporation is developed here to remove unwanted solvent(s) and optimize the transfer to the second dimension without jeopardizing resolution and sensitivity by (i) dilution of the sample and/or (ii) mismatch of the injection solvent with the second dimension separation. The interface consists of a heater module with a sophisticated on-line feedback system for removing unwanted solvent and a computer controlled nano-liter sampling valve. The development of the heater and valve module has progressed to the point where the various parts are now ready for integration of the different modules. We are currently able to successfully evaporate 50 – 5000 nL/min organic effluent flows and handle 80 nL of sample with the designed valve. The interface being developed will allow the LCxLC analysis of metabolites in complex mixtures without the current problems of solvent incompatibilities in the transfer from the first to the second dimension.