Chromatography Forum

For small molecule work looking at reaction mixtures (Mostly polar water soluble compounds) trying to figure out side products as well as looking at expected products, outside of price, what are the relative advantages/disadvantages of a QTOF vs a triple quad?

So far I have been using a a QToF for intact proteins (my only LC/MS experience) but we will also be moving into a different type of small molecule work as well. While I think this new work could be done OK on the existing QTOF, that will be tied up on another project so we may need another instrument.

I think Triple Quads are cheaper than QToFs, but from what I've read it seems QTOFs are better when having to deal with unknowns.

Thanks for any feedback

Think you will need to add a little more info. for a definitive answer

If by small molecule you mean a few hundred AMU then a Q-TOF will be beneficial for identifying unknowns if it offers accurate mass capability. e.g. Pfizer have a number of Bruker Q-TOFs as not only do they offer accurate mass but with Smartformula3D they identify all their components without having to carry out any additional interpretation.

Triples are generally still more sensitive than Q-TOFs for targeted compounds but that's no use for unknowns.
You may not wish to disclose on an open forum what you are actually interested in, call your local suppliers and ask them, here in the UK Bruker have a number of application specialists who can discuss your application in confidence. Other suppliers may offer similar.

To compare QQQ vs QTOF

QQQ
Selectivity by MRM (Target)
Linearity for Quantification +++
Sensitivity +++
number of target +

QTOF
Selectivity by MRM, High Resolution EIC (Suitable for Unknown Analysis)
Linearity for Quantification +++
Sensitivity ++
number of target +++(++)

Jetjamnong, what do you mean by "number of target"?

Sorry, I means the number of target compounds on time segment.

I'd imagine it's also a matter of how efficiently the duty cycle is used for your needs.

If you're doing a bunch of product ion spectra, great, you can send a packet of ions from the Q through to the TOF and get the full spectra for fragments.

If you're doing a large number of MRM transitions from multiple molecules, on the other hand, a QQQ can cycle amongst them more efficiently; on a QTOF the Q selects the precursor and then has to wait for a full spectrum of fragments to pass through the TOF before it can do anything with the next precursor.

I would imagine that with small molecule quantitation the Q-TOF is good for initial method development, but once you know all your fragments and you want to make a routine method out of it, it might be best to transfer to the QQQ.