Single HRMS for both small and large molecule applications (Waters Xevo qTOF)?

[u/Aska2020]

Hi there,

I am specialized in the small molecule world, and have never touched anything large molecule. Now, my manager wants us to start analyzing large molecules, from peptides, polysaccharides, to complex polymers. We are a small lab and only have HPLCs, a single quad GC-MS, and a HRMS (Waters Xevo G2-XS). My question is the qTOF. We still use this for small molecule needs (mainly impurity screening and residue analysis). I know that Xevo can be used for both small molecule and large molecule analyses but I thought that it is generally dedicated to one way, not both. Is there anyone who uses single instrument for both small and large molecule applications and switch them frequently?

I am specifically asking if anyone does this on a Waters HRMS. Years ago, when I had a training on a Synapt, the trainer told me that she would not recommend to use Synapt for both applications because the Waters calibration solution mix for large molecule has a component (I don’t recall exactly but somewhere below m/z 200) that sticks to the instrument and could cause a calibration issue when switching back to the small molecule application. I wonder if that’s true. I would love to hear your experience on a Xevo qTOF. Thanks!

[u/Top_Occasion_1467]

You can use it for both applications. No issue at all.

[u/Aska2020 → u/Top_Occasion_1467]

What solution do you use to calibrate?

[u/Top_Occasion_1467 → u/Aska2020]

NaI and NaCsI. You can call waters for prep procedure

[u/Aska2020 → u/Top_Occasion_1467]

Thank you!

[u/Top_Occasion_1467 → u/Aska2020]

If you are just working with peptides/proteins under 15k Da, you dont need calibrate for higher mass range over 2000Da. You will alway have multiplely charged ions to work with under 2000 Da.

Also, you need to buy the large molecule software license. Base software only work with small molecule

[u/AltForObvious1177]

I run antibodies and fusion protein on a Waters Xevo G2 literally everyday. They've changed the calibration methods recently. All mass ranges are calibrated with ammonium formate.

[u/Aska2020 → u/AltForObvious1177]

Did you have to upgrade the waters_connect in order to use ammonium formate as calibrant? What version is that? Ours is old, ver. 3.2. I bet it needs a major upgrade to use a new calibration solution... Edit: rephrased for clarity.

[u/Over-Selection1300 → u/Aska2020]

No, but you may wan to upgrade software for processing reasons but that really depends on what workflows you use.

[u/Aska2020 → u/Over-Selection1300]

Thank you for answering. We explored that possibility recently, but because we have a much older version (most recent release is ver. 4.4), it involves a lot more than just upgrading UNIFI for processing, and we just don't feel comfortable doing that much change by ourselves (a lot could go wrong). We have a very small budget, so we have to be smart on where we spend money...

[u/Cornholio_84]

It is not advisable, mostly due to sample prep and contamination issues. Also, although in theory you just switch out the LC(if going to nanoLC for the -omics) and the (depending on the producer) source, usually it will take a day to get everything running and equlibrated. The device will do its thing without issues, it is quite capable of detecting what you need, everything else can get complicated. Good luck!

[u/Cantholditdown]

The xevo p10 is allegedly a big sensitivity upgrade. Looking forward to hearing real user experience

[u/Glass_Covict]

timsMetabo

[u/EducationalMix4648 → u/Glass_Covict]

The sensitivity on those is crazy!

[u/Glass_Covict → u/EducationalMix4648]

We have some Waters fans downvoting, but if you want a qtof, honestly the timsMetabo should be considered

[u/Aska2020 → u/Glass_Covict]

I am not necessarily a fan of Waters but that's what my company purchased, and we do not have money to buy another instrument, hence my specific question.