Multiple solid-phase microextraction (SPME) is an useful technique for the direct quantification of solid samples removing any matrix effect. The volatile organic compounds formed in the extrusion-coating process of multilayer packaging materials have already been quantified by multiple HS-SPME coupled to gas chromatography (GC)-mass spectrometry (MS) using volatile organic compound (VOC) solutions in hexadecane for calibration. In this article, water is proposed as solvent to prepare the calibration solutions because it provides a shorter calibration time, better linearity, better reproducibility, and lower detection limits than hexadecane. Besides, the extraction of VOCs from aqueous solutions is exhaustive and avoids the extrapolations needed to calculate the total peak areas, as they can be calculated as the sum of the individual areas of each extraction. Finally, it is checked whether the two solvents provide the same mean values for the total peak areas.