Methods are provided for the preparation of a sample using a digital microfluidic platform and the optional subsequent mass analysis of an extracted analyte. A sample is dried, optionally on a solid phase support, and contacted with digital microfluidic array. An analyte present within the dried sample is extracted into an extraction solvent by electrically addressing the digital microfluidic array to transport a droplet of extraction solvent to the dried sample spot. The extracted sample may be dried and subsequently processed on the digital microfluidic array for derivatization. The digital microfluidic device may further include an integrated microfluidic channel having an output aperture, and the method may further include contacting a droplet containing extracted analyte with the microfluidic channel and applying a suitable electric field for generating nano-electrospray, thereby enabling the device to be directly interfaced with a mass analysis device.