During the past decade, e-cigarettes have become increasingly popular. To guarantee their safe use and to comply with the notification requirements of the EU Tobacco Product Directive, the EU member state regulatory authorities need information about the exact composition of the e-liquids and their emissions. However, one of the challenges encountered during the analysis of e-liquids is the presence of the highly abundant e-liquid matrix components propylene glycol and glycerol. In this study, headspace gas chromatography (HS-GC) analysis is presented as an excellent method for the analysis of high volatile components in e-liquids. For the analysis of semivolatile ingredients, an additional sample preparation step is proposed based on a liquid–liquid extraction (LLE) followed by a freeze-out of the matrix components. The developed method was successfully validated in accordance with the validation requirements of ICH guidelines for the quantification of four flavourings with a potential health concern for e-cigarette users.