A total of 15 standard compounds with structures similar to those normally found in crude oils were analyzed using an ultrahigh-resolution and high-accuracy Fourier transform ion cyclotron resonance (7.2 T LTQ FT Ultra, Thermo Fisher, Bremen, Germany) mass spectrometer. Four different ionization techniques were used: electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI), and a novel technique that couples APCI and APPI, herein termed atmospheric pressure photo- and chemical ionization (APPCI). Relationships between chemical structures and ionization efficiencies were established for these techniques, which operate via different ionization mechanisms. The unsaturation level and position of the double bond were shown to be key factors on ionization efficiency for all ionization techniques. Comparisons between molecules with similar backbones but with different heteroatoms were also made. For the whole mixture, APPI showed the highest sensitivity for the positive ion mode and ESI showed the highest sensitivity for the negative ion mode. APPCI was found to be the most comprehensive ionization technique, whereas as expected, ESI preferentially ionized the most polar compounds. APPCI produced, however, more than one ionic species per molecule, a disadvantage in terms of data complexity. Such "splitting" was observed for APPI and APCI. Ions with the same molecular formula formed from different molecules were also detected by APPCI, producing composite abundances that would mislead chemical and geochemical conclusions based on petroleomic approaches. We suggest that, although less comprehensive, ESI is overall the most suitable ionization technique for petroleomic studies.