The popularity and regulation of electronic nicotine delivery systems (ENDS) has drawn attention to the chemical composition of the e-liquids used in, and aerosols formed by these devices. The possible presence of carbonyl compounds like formaldehyde, acetaldehyde, diacetyl, acetylpropionyl, and acetoin are of concern due to their potential impact on human health when inhaled at sufficient concentrations. Flavoring added to the e-liquids may contain diacetyl, acetylpropionyl, and acetoin, which can be easily transferred to the aerosol. Propylene glycol and glycerin, the main carriers used in e-liquids, are heated during the formation of the aerosol and may undergo thermal decomposition leading to the formation of formaldehyde and acetaldehyde. Analytical detection of carbonyls is commonly achieved by analysis of their corresponding 2,4-dinitrophenylhydrazine (DNPH) derivatives using liquid chromatography. This method can be problematic in this complex matrix due to the possibility of interfering peaks and can result in incorrect reporting of data. The objective of this study was to develop a single rapid method for accurate detection and analysis of carbonyls that may be present in flavored e-liquid and aerosol samples. A method of determination of carbonyl compounds by ultra-performance liquid chromatography (UPLC) and electrospray ionization (ESI) tandem mass spectrometry (MS/MS) after derivatization with DNPH was developed and successfully applied to the evaluation of e-liquid and aerosol samples. This method allows for the detection and analysis of carbonyls including formaldehyde, acetaldehyde, acetone, diacetyl, acetylpropionyl, acrolein, acetoin, and crotonaldehyde in e-liquid and aerosol samples in less than ten minutes. The LC-MS/MS method will be compared to an existing UPLC method with an emphasis on its application to the analysis of complex, highly flavoured samples.