I was under the same impression for untargeted. Some reported using really expensive isotopes for each group (up to £300 for 20mg) and I don't see how it added to the analysis?
I have also considered using a chromatography check solution at the start and the end of each run to check that this is taking place properly, is this overkill taking into account I will be putting multiple pooled QC's throughout?
From my background reading it is suggested you use internal standards in each LC-MS sample in order to improve the quality of data analysis. However, one of the examples given is of ~8 isotopic compounds such as L-lysine d4 of which many are very expensive and others do not mention what the internal standards are. Is there a minimum number of standards required for a robust experiment or are they specifically dependent on the experiment itself? I currently use pooled QC samples and use reference compounds to calibrate the machine but nothing else.