Recently, the formation of carbonyl compound within e-cigarettes usage has been reported. The aim of this study was to develop a new analytical method for the direct analysis of carbonyl compounds in vaporized liquids. Two different types of e-cigarettes and different puff’s duration have been evaluated, using a modified smoking machine for vapor generation. An isotopic dilution approach, based on deuterated internal standard addition to the e-liquid before filling the e-cigarette tank, has been developed. Carbonyl compounds have been sampled in vapors using a direct, simple, solid-phase microextraction technique with on-fiber derivatization. Related oximes have been analyzed by gas chromatography/mass spectrometry technique. Results confirmed that new carbonyl compounds are formed during the vaping process, and that formation depends both from the heating device and from puffing topography.