The coupling of liquid chromatography to mass spectrometry (LC-MS) was only studied from 1974 onwards, due to much greater technical difficulties than for gas chromatography coupled to mass spectrometry (GC-MS), available as standard on commercial equipment as early as 1968 – see Chromatographic couplings with mass spectrometry. II
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. For ten years or so, a wide variety of LC-MS devices were proposed, but from 1986 onwards, the development of atmospheric pressure ionization sources for mass spectrometry removed most of the obstacles to the development of LC-MS.
LC-MS coupling is currently one of the most powerful analytical tools available to chemists and biochemists. This technological revolution began in the 1990s, with the emergence of reliable commercial instruments based on the atmospheric pressure ionization methods (API-MS) discovered by the American John Fenn in the previous decade. The award of the 2002 Nobel Prize in Chemistry to John Fenn, shared with Japan's Tanaka for the discovery of MALDI, was testimony to this breakthrough.
Today, this type of coupling accounts for the majority of commercial instrument sales, and enables us to successfully tackle the most complex analytical problems, particularly in analytical biology (for example, protein characterization and sequencing). While liquid-phase separations on reversed-phase columns are the most frequently used, as they have been since the early days of LC-MS coupling, many other separative techniques are now coupled directly to mass spectrometry, notably those operating with high electric fields. In fact, manufacturers today refer to LC-MS as a mass spectrometer capable of sampling analytes in liquid solution – whether or not derived from an on-line separative method or from a preparation device.
LC-MS couplings are included as major chapters in all recent mass spectrometry textbooks