Several chromanol drug substance candidates exhibit unconventional behavior under the soft ionization conditions of fast atom bombardment and electrospray ionization in the mass spectrometer. Under FAB, these compounds produce radical cation molecular ions rather than protonated molecular ions. Similarly, under acidic mobile phase conditions in an electrospray LC-MS experiment, they produce radial cation molecular ions. Upon changing to a neutral, ammonium acetate-containing mobile phase, the molecular ion species is an ammonium adduct. The two example compounds behave conventionally under negative ion detection, both being free carboxylic acids and forming abundant [M - H](-). Examination of structural analogs indicates that the chromanol, methoxyl and chroman compounds behave this way. Oxidation to a chromanone causes formation of a conventional [M + H](+). Oxidation to a chromene produces even more complex behavior-namely a mixture of [M - H](+), M(+') and [M + H](+). We propose that, for these compounds, elimination of a valence electron to form the radical cation is the more energetically favored reaction than attachment of a proton.