Measuring the mass of an electron by LC/TOF-MS: a study of "twin ions"

While investigating the in-source CID fragmentation of nonsteroidal antiinflammatory drugs (NSAIDs), it was noticed that the same fragment ion (nominal mass) formed in either positive or negative ion electrospray for a suite of NSAIDs. For example, ibuprofen with a molecular mass of 206, fragments to the m/z 161 ion in negative ion from its deprotonated molecule (m/z 205, M - H]-) and fragments to the m/z 161 ion in positive ion from its protonated molecule (m/z 207, M + H]+). This fragment ion was euphemistically called a "twin ion"because of the same nominal mass despite opposite charge. The CID fragmentation of the twin ions was confirmed also by LC/MS/MS ion trap. Accurate mass measurements in negative ion show that the loss was due to CO2 (measured loss of 43.9897 atomic mass units (u) versus calculated loss of 43.9898 u for N = 10) and in positive ion the loss is due to HCOOH (measured loss of 46.0048 u versus calculated loss of 46.0055 u, N = 10). It was realized that, in fact, the ions were not "identical mass twins of opposite charge" but separated in accurate mass by two electrons. The accurate mass measurement by liquid chromatography/time-of-flight-mass spectrometry (LC/TOF-MS) can distinguish between the two fragment ions of ibuprofen (161.13362 +/- 0.00019 and 161.13243 +/- 0.00014 for N = 20). This experiment was repeated for two other NSAIDs, and the mass of an electron was measured as the difference between the twin ions, which was 0.00062 u +/- 14.8% relative standard deviation (N = 20 analyses). Thus, the use of continuous calibration makes it possible to measure the mass of an electron within one significant figure using the NSAID solution. This result shows the importance of including electron mass in accurate mass measurements and the value of a benchmark test for LC/TOF-MS mass accuracy.