Coupling chromatography with mass spectrometry - Part 1

The very principle of chromatography is to separate the constituents of a mixture to be analyzed. The chromatographic column selectively delays the progression of solutes which, when separation is successful, exit the column in successive order.

Modern instrumentation is faced with increasingly complex analyses, due to the large number of constituents present and the extremely small quantities to be detected. What's more, these analyses have to be increasingly rapid and automatable in order to deliver results for a very large number of samples.

Classic examples of complex media with these characteristics are biological media in general, petroleum cuts, essential oils and atmospheric pollutants. It is not uncommon to want to identify and quantify a single product in the mixture, present in traces representing one part per billion (ppb) of the total sample.

There are countless applications in a wide range of economic sectors, such as industrial product quality control, fraud control, anti-doping and environmental monitoring, ....

While chromatography alone enables the correct separation of the various constituents of a mixture, it is nevertheless a delicate task to make a structural interpretation that allows certain identification, as the parameters deduced from the selective retention of solutes through the column are often unwieldy and, in most cases, linked in a complex and indirect way to organic molecular structures.

The idea of coupling another physical method of investigation, after chromatographic separation, in order to add a second analytical dimension to chromatography, took shape as early as 1960 with the combination of gas chromatography and mass spectrometry (GC-MS).

The coupling of liquid chromatography and mass spectrometry (LC-MS) was not studied until 1974, mainly because of the much greater technical difficulties involved. The development of atmospheric pressure ionization sources for mass spectrometry, from 1986 onwards, removed most of the obstacles to the development of LC-MS.

The search for rapid analysis methods that can handle an increased number of samples, and the need for continuous real-time monitoring, have also led to the development of integrated rapid methodologies in which the chromatographic step is either accelerated or eliminated altogether and replaced by automatic sample handling processes.

These separative methods are generally associated with the chromatographic method set, and can often be connected to mass spectrometry.