Ion chromatography (IC), when coupled to mass spectrometry (MS), offers an alternative to the analysis of ionic or highly polar compounds using LC-MS.
IC-MS has a broader range than HPLC-HILIC; it is also more robust and reproducible than HILIC.
The high resolution that is inherent with IC has led to the differentiation of many isobaric and isomeric polar metabolites via IC-MS, including sugar phosphate isomers.
IC can be easily integrated with mass spectrometry because analytes are often provided in the ionic form needed for MS detection. By adding suppressor technology, standard IC eluents and methods can be used. Also, the suppressed background is composed of pure deionized water, allowing easy and advantageous switching between anion and cation feed into the mass spectrometer.
IC-MS may be used in both untargeted metabolomics and in targeted metabolomics workflows.
IC-MS workflows are similar to those of LC-MS and, unlike GC-MS workflows, offer no spectral libraries for compound identification. However, because molecular ions are usually present in IC-MS, they can be used as part of the compound identification strategy. To begin with, ions can be used to search a database of metabolites such as the METLIN database. With recent advances in HRAM MS systems, it is now possible to calculate the empirical formula of a target compound from the molecular ion.
To better elucidate unknown metabolites, the molecular ion can be fragmented by MS/MS, and MS/MS spectral libraries can be compared and matched. Quite often, this does not lead to a confident identification, and further MS (MSn) analysis is needed. Following MSn, manual de novo interpretation/structural elucidation can be performed as part of the identification process.