No principally different optimization is needed, that is you can easily analyze any components in your tripleQuad system. However signal intensity (sensitivity) would certainly depend on the parameters you use for different classes of compounds. Especially pay attention to solvents. Peptides are best in formic acid - positive mode. 

>>When we do direct infusion of peptides to optimize for collision energies, we tend to get high signal for some small m/z's which does not match the peptide b/y fragmentation.

There are many other fragments you can always see in addition to exact b and y (e.g. +18). And actually if you go high enough with CE you would get secondary and so on fragmentation (which would certainly be not b and y ions), and if you go high enough you can crack aminoacids as well, in which case you would get high intensity ions of "unknown" origin (actually just no peptide-bond fragmentation ions) in low m/z region. 

You can see this effect increasing CE: m/z fragmentation distribution would gradually shift from covering all m/z region to narrower and narrower m/z region in low m/z. 

The low m/z fragments might provide the most intense signal when you run an instrument optimization, however they are not highly sequence-specific and as such will often lead to poor S/N in complex backgrounds. You usually want b/y type ions with m/z above the precursor which optimize at low-to-moderate CE, are highly sequence-specific and provide best m/z in complex backgrounds. 

Talk to Bruker if they have any specific sensitivity tests for your specific QqQ model and LC setup. Most instrument vendors are a bit shy on publishing these tests and rather use small organics like reserpine or busporine to spec and test their systems, however if you insist then they should at least provide you with data to compare against, if not specific specs.

Sergey Kovalchuk's comments are good ones.  Any good mass spectrometer will work well for beither peptides and metabolites, but it's not as simple as just changing what you inject.  For example, of you're looking at metabolltes in negative-ion mode and then switch to positive mode for peptides there will be a loss of sensitivity (at least for a while).  With respect to what 'other' labs report, remember that they may have long-time experience in peptide analysis and are just very good at it.  When you do direct infusion, is this with peptide mixtures or with pure peptides?  With mixtures, there may be ion suppression and the signals chosen for MS/MS may not be from unique peptides.  As with anything, it takes practice!   Don't be too hard on yourself (or the instruments), and don't be in too much of a hurry.

Thanks for all the replies! 

I guess I should not be bothered by the small m/z's but rather go for the targeted masses when doing CE optimization. If I understand correct, I will always get some high intensity small m/z's when we ramp up the CE energies during the optimization, as we fragment everything eventually. 

Still we have the problem with the low intensities of peptides, even when we do direct infusion to optimize for the targeted fragmentations (indeed the CE voltages are lower when going for targeted optimization). 

We are using a mixture of 20 synthetic peptides for our optimization, and we have these peptides in 50 % MeOH and 0.5 % FA. Would you still be concerned about ion suppression for such a "low complexity" sample?  

By the way, what do you mean by low intensities? What peptide concentration do you use? What is your injection parameters? Nano or Micro spray? What kind of peptides do you use? Every peptide has its unique concentration-to-signal ratio, thus it is theoretically possible that all your 20 peptides are not very good ones for ESI. It can really depend on their AA sequence. 

Ion supression has nothing to do with sample complexity. It can happen even for two peptides mixture, if they coelute in HPLC or you just inject them together, and one of them would suppress ionization of the other. More problems with ion supression arise when you do not know for sure peptide composition of your sample. And when you do MRM experiment you have no idea whether there is anything coeluting with your target peptides (you just do not control MS1 signal to know whether there is anything else coeluting), which might interfere with them.

Actually, ion supression in ESI is a tricky thing, much more so than in MALDI. But anyway, even if you have ion supression for one component you should see another component so much clearer. Besides, you are supposed to see both peptides whatever, with just lower intensity for one of them in comparison to this peptide alone.

Very low m/z region is absolutely useless for peptide MRM, since it is not specific at all. I would recommend do not even measure this region when doing CE ramping for fragmentation optimization. You can start with m/z 100-150. Actually, when you go to more complex samples for your MRM analysis the higher m/z you use for fragment ions in MRM transitions the less background noise you would get. Some people recommend to use fragment ions with m/z higher than parent ion m/z. Well, if you have such fragments - perfect. But usually they are far from being the most intensive transitions. And either you get lower background for high m/z but low intensity transitions or you have high background for low m/z but high intensiity transtions you would end up with the same signal-to-noise ratio that is the ultimate estimation of your sensitivity and selectivity. 

Hi Daniel,

as the others told you the MS instruments iare able to analyze both metabolites and peptides. However, the instrument has to be tuned accordingly. Additionally, you have to use a nano LC for peptides and also a nano ESI source to gain sensitivity. If you have a micro LC, you need much more material to get the same signal intensity.

I can't tell you any specific adjustments for Bruker instruments because I work with Thermo Orbitraps for Proteomics. Thermo has a normalized collision energy which is not similar to the one Bruker is using.

Maybe the best program to analyze SRMs of peptides is Skyline:

https://brendanx-uw1.gs.washington.edu/labkey/project/home/software/Skyline/begin.view

It is an open source software. The newer versions can be also used with Bruker files as far as I know. This software has also some optimization features for method development (at least it has for ABI triple -Quads). There are a lot of tutorials online.