Some people in California have been investigating whether we need all this fancy hardware for targeted analysis. They started with metabolites, but - hey - why not extend it to peptides?
It all comes down to confidence metrics, right? Is this your molecule of interest? How many points do you need to prove it?
Some people go all the way one direction where they have:
Molecule retention time
Exact mass (or mass out to 3 decimal places)
Exact mass of every fragment ion (or out to 2 or 3 decimal places)
Increasingly, they also have ion mobility values of some kind (I'd go so far as say that FAIMS should count here)
And maybe they even have internal standards
This is obviously superb and amazing and extremely high confidence AND ABSURDLY EXPENSIVE. Good for you if you've got the cash, but I'm in the U.S. and we need to make sure that extremely wealthy people get paid every time we need a medical test.
If we want proteomics in the clinic, we need to cut costs all over the place. Years ago I was told $8 needs to be the target for an assay that can be billed to a patient for $800. Those costs have ballooned out, but it's tough to get there when you start with a $1 million dollar instrument.
Start with a $60k single quad? Now you can start talking about new assays that will make enough profit for hospital administrators and insurance companies that they'll let you even try to help patients.
The specificity in these matrices is suprisingly good. I highly recommend this study.