Structure elucidation by LC-MS. Foreword

Abstract

The topic of this Analusis Dossier is structure elucidation by liquid chromatography -mass spectrometry (LC-MS). When LC-MS first came along in the mid 1970's [1], one of the incentives and objectives was to develop a technique similar to the very successful gas chromatography -mass spectrometry (GC-MS), but capable of identifying especially those components which were not amenable to GC-MS. To that end, interfaces were developed, aiming at the application of electron ionisation (EI), like in GC-MS. Although these interfaces like the moving-belt and the particle-beam interface actually demonstrated that the applicability range of EI could be significantly extended, ironically enough these two interfaces did not achieved the major breakthroughs in the development of LC-MS.Major steps in the history of LC-MS were made using interfaces that only allow soft ionisation techniques, resulting in (de)protonated molecules with little or no fragmentation. Thermospray interfacing from the mid 1980 onwards for the first time gave a glimpse on what LC-MS could really do. With the broad implementation of the atmospheric-pressure ionization and interfacing, viz. (pneumatically-assisted) electrospray ionisation and interfacing (ESI) and the heated nebuliser in combination with atmosphericpressure chemical ionisation (APCI), LC-MS became a powerful technique which could even be used by less experienced people. However, in addition, the most frequent use of LC-MS today is quite different from the initial objective indicated above. LC-MS has significantly changed the impact of MS in a laboratory, because with LC-MS the mass spectrometer has entered both laboratories and application areas in a way which was certainly not foreseen at the beginning of its history in the mid 1970's [2]. Especially the large interest in routine quantitative analysis and peptide and protein analysis was not anticipated.With LC-MS being based on soft ionisation techniques, the development of LC-MS to some extent stimulated the developments in tandem mass spectrometry, especially in triple-quadrupole and ion-trap instruments. With the ability to fragment the even-electron protonated or deprotonated ions, generated in ESI and APCI, by means of collisioninduced dissociation (CID), the first steps in the direction to structure elucidation could be made. However, soon it was realised that in fact there is far less knowledge on the fragmentation of these even-electron ions compared to that of odd-electron ions [3], as generated in EI. Despite the fact that many authors tried and still try to cover this by incorrectly calling the (de)protonated molecule a '(de)protonated molecular ion ' [4], this difference is obvious and important when one starts to interpret the MS-MS product-ion mass spectra. In addition, the interpretation of the product-ion mass spectra must actually be performed, because no spectral libraries were available which could be used to assist in the structure elucidation. Fragmentation of even-electron ionsIn the past 14 years, ever since my pr...

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