It looks like almost all the untargeted metabolomics data are produced by high resolution instruments. Can we still use ion trap or QqQ instruments for acquiring untargeted metabolomics data? Could anyone please list out or explain for not using low res. instrument (for example Thermo Vantage) for untargeted analysis?
In untargeted you need to be able to identify the compounds/peaks/features that are significant after data analysis. If you don't have accurate mass this becomes very difficult and I guess in many cases impossible. The days where you can publish a metabolomics paper without a reasonable number of identifications are over.
Another issue is separating co-eluting (but different) features with same nominal mass.
Exact knowledge of a neutral loss, for example, may be essential to identify an unknown molecule that arises as a differential feature. See a single example: H2O and NH4+ both have an m/z of 18 in a low resolution instrument, but you can distinguish between both with a high resolution instrument because water is 18.01 and NH4+ is 18.03.
You can use low resolution MS such as a QQQ to confirm (by quantitation) the findings of a untargeted metabolomics experiment. Untargeted experiments are inherently complex and identification of metabolites still difficult even with high resolution MS due to lack of adequate MS/MS databases, differences in instrumentation, biases made in sample preparation, etc. I would say the chance to identify a metabolite based on low resolution MS is very close to zero, although there may be cases where MSn in an ion-trap may help the identification. However, HRMS is required to calculate a molecular formula. Even with a mass accuracy of 1 ppm you could have many possible identifications. The example above illustrates what accurate mass can do for you although if we compare the neutral losses of water and ammonia (ammonium is not a neutral loss since it is an ion) the mass difference is substantial and can be seen even with a low resolution MS (18.01 for water vs 17.03 for ammonia). Here is an arbitrary example of an ion with m/z 413.2662 in an Orbitrap. For a mass accuracy of 1 ppm with only C, N, O and H considered as possible elements we obtain only one molecular formula: C22H33O2N6, if we consider a mass accuracy of only 10 ppm then 7 molecular formulas are possible with the same elemental composition. Perhaps the MS/MS would be able to eliminate half of these but you would still have multiple choices for which a synthetic standard would be required to be able to correctly identify the compound.
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