Why mass spectrometry is also a quantitative method?

Mass spectrometry coupled with liquid chromatography is used for several decades as qualitative tool for molecule characterization thanks to its ability to detect specific molecular weight.
With the improvement of the instrumental technology, it has been implemented in bioanalysis for small molecules as the gold standard for quantitative analysis for routine food testing, forensic but also for pharma pre-clinical, clinical analysis.
For many people, mass spectrometry is only seen as an identification tool. But this technique is a powerful quantitative instrument that can be really relevant for number of applications (host cell proteins, vaccines, therapeutic proteins…).
Mass spectrometry is often seen as an analytical tool for experts only. Quite a few complicated terms referring to different techniques (peptide mapping, DDA, DIA, shotgun, MRM, SRM…) are used and it might lose non expert people.

So let’s make it simple. Mass spectrometry (MS) may be split in 2 categories:

• global mass spectrometry
• targeted mass spectrometry

And to make even clearer, we will use the famous iceberg concept.

Imagine that the global MS is like having an overview of your iceberg, you look at the tip. It gives you an overview of what you get in your sample and gives you some proportion. But this approach brings limited sensitivity for low- abundance analytes and you may miss some relevant protein.
Furthermore, as it depends on how the waves lick the iceberg, you won’t see exactly the same thing between two experiments (between 60% to 70% recovery in global analysis). So it leads to a lack of reproducibility of identifications and a poor consistency in quantification for low concentrated compounds. Of course, the impact on high concentrated ones is limited, like your iceberg vision. Moreover, you will get a lot of information and you will need to have the adapted tools to deal with them. In this case, indeed, experts are often mandatory.