Gas Chromatography-Electron Ionization-Mass Spectrometry (GC-EI-MS) is still the most routinely performed method for metabolite profiling as compared to other hyphenated techniques. But when it comes to identification of unknown compounds, information on the molecular weight is not readily available because the molecular ion is not always found with electron ionization (EI). Thus, the use of chemical ionization (CI) is envisaged that commonly produces the molecular ion; in combination with accurate mass measurement, this technique would further allow for calculation of sum formulas of those compounds. However, for proper accuracy of analysis, a mass calibrant is needed. We set out to find a commercially available reference material with mass peaks that would qualify the substance as mass calibrant under CI conditions. Six commercially available mass calibrants, FC 43, PFK, Ultramark 1621, Ultramark 3200F, Triton X-100, and PEG 1000, were tested under CI conditions to understand their fragmentation behavior. Our findings indicate that Ultramark 1621 and PFK best fit the expectations of a mass calibrant for HRMS analysis whereby PFK provided a fragmentation pattern similar to EI outcomes thus enabling the use of mass reference tables commonly provided within commercial mass spectrometers. On the other hand, Ultramark 1621 is a mixture of fluorinated phosphazines that shows stable fragment intensities.