Table 3.

Limitations of MS‐based structural elucidation

Limitations and pitfalls in ESI‐MS based structural elucidation
1. Not all compounds ionize by ESI and, thus, can be detected in MS (or only in positive or negative mode).
2. The MS signal is spread over different isotopes, adducts, and/or fragments.
3. The MS response is highly dependent on the chemical structure of the compound.
4. The nature and abundance of the ions (adducts, fragments) is highly dependent on the sample solvent and matrix and the instrumentation hardware, settings and, overall, the experimental conditions used.
5. Not all peaks in an MS spectrum are necessarily from the compound of interest: there can be interferences from chemical and non‐chemical (noise) background.
6. Product ions that originate from a rearrangement or loss of a part of the molecule appearing as unchanged compared to a reference molecule, can be misleading.
7. Isomers like enantiomers and rotamers cannot be differentiated with MS alone.
8. Salt forms cannot be assigned with ESI‐MS.
9. Structure elucidation with MS often leads to partially assigned structures (ie, Markush structures) rather than fully identified structures (eg, for regio‐isomers).