Truly “exact” mass: Elemental composition can be determined uniquely from molecular mass measurement at ∼0.1 mDa accuracy for molecules up to ∼500 Da

At sufficiently high mass resolution, not all molecular masses are possible, even for arbitrary elemental composition. Here, we consider all possible elemental compositions, CcHhNnOoSs, c unlimited, h unlimited, 0 < n < 5, 0 < o < 10, 0 < s < 3, for even-electron ions (M + H)+ and (M − H)−, of molecular mass, 300–500 Da. Masses are then sorted into “bins” of width, 5, 1, 0.5, and 0.1 mDa, with inclusion (or not) of up to two 13C's. The number of different elemental compositions per bin varies from 0 to ∼20 for 5 mDa bins, dropping to 0–2 for 0.1 mDa bins (including one 13C) and 0–1 for 0.1 mDa bins (not including 13C). Thus, for molecules up to ∼500 Da in mass, mass resolution and accuracy of ∼0.1 mDa generally suffice to yield a unique elemental composition for molecules in even the most complex natural mixtures (namely, petroleum crude oil), and higher mass resolution and accuracy are not necessary. The required resolution and accuracy are now becoming available with high-field (9.4–14.5 T) Fourier transform ion cyclotron resonance mass spectrometry.