Comprehensive two‐dimensional gas chromatography (GC×GC) coupled with mass spectrometry (MS) is one of the most powerful analytical techniques now available for detailed analysis, identification and quantitation of medium‐to‐high complexity mixtures. However, the number of application methods that combine fingerprinting and/or profiling with quantitation of informative volatile analytes (targets) is still limited. Possible reasons are related to the huge amount of information to handle and to the availability of reference standards for calibration. Although quantitative analysis by GC×GC is complex it has important advantages: (i) to assess data/results over an extended time frame, varied instrumentation and different laboratories; (ii) to interpret the biological role of (potential) biomarkers; (iii) to evaluate the impact of potent odourants; and/or (iv) to define product quality, e.g. relative to a reference standard. In this study, a GC×2GC‐MS/FID platform consisting of one primary column (1D) coupled to two parallel secondary columns (2D) having an identical inner diameter, stationary phase chemistry and film thickness, which, in turn, are connected to two detectors: a fast quadrupole MS and a FID, was adopted for quantitative profiling of essential oils (EOs). Two medium complexity EOs (i.e. Mentha and Lavandula species) that pose different quantitation challenges were taken as examples and a selection of quality markers subjected to an extensive method performance evaluation (e.g. method validation). Experimental results confirmed the platform's reliability in terms of: linearity, precision and quantitation accuracy. In addition, predicted FID Relative Response Factors (RRFs) based on combustion enthalpies were adopted to extend quantitation to all identified analytes. The experimental data demonstrated the accuracy of the predicted RRFs, supporting their adoption in quantitation of EO markers. This approach is of particular interest for those applications where reference standards are not (easily) available and/or regulated. Copyright © 2015 John Wiley & Sons, Ltd.