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Topic: Suggestion to purchase of a high-resolution MS (Read 1716 times) previous topic - next topic

Suggestion to purchase of a high-resolution MS

We plan to buy a high-resolution LC-MS system with enough dynamic range for quantification.  Currently, our applications are focused on small-molecule drug metabolism.  We particularly care about robustness.  We also care about performance, software, database, etc.  It will be highly appreciated if anyone can message me direct user experience from you and your colleagues/friends.  The experience from either one or multiple models of instruments will be helpful.  Thanks.       

Re: Suggestion to purchase of a high-resolution MS

Reply #1
Hi Sam,

I don't have a lot of HRMS experience, but I've gradually been doing more. Our focus is high-throughput, so robustness is something we care about as well. As a general rule, the top spec instruments tend to be less robust than the lower tier models, although there are always exceptions.

So far I've used an Agilent qTOF (6540) and two Thermo Orbitraps (Fusion Lumos and HF-X). All of these were setup to do analytical flow LC-MS.
The Agilent system had quite a few boards replaced over a few years, but I can't say that the instrument was looked after particularly well.
The Fusion Lumos ran well for over 1000 continuous samples (plasma). But other than that, I am not sure how robust the machine is outside of that.
The HF-X had a bad reputation for 'dirtying', but Thermo says they have fixed this in the current generation. If you are willing to wait a few months I can fill you in on how it goes :)

For the work that I was doing (lipidomics), the much higher resolution given by the orbitrap was very useful. Overall sensitivity was higher with the orbitraps as well - but we are comparing 2 very new instruments to a much older one.
However, both the orbitraps have very rough ion funnels. This causes in-source fragmentation of fragile molecules. This isn't exclusive to Thermo instruments.
Most vendors are aware of this, so you should bring it up with them if this is a concern.

Regarding quantitation, there are different levels of quantitation that people expect. Most metabolomics/lipidomics people have a relaxed view on quantitation. That is, there are caveats and assumptions that everyone excepts can't be resolved (not enough internal standards, shotgun vs LC...)
Most newer instruments provide a fairly decent dynamic range. Certainly much more than the expected variability you would see in a single metabolite in a group of people. So I guess it's important to ensure that sample prep is correct to put the right amount of 'stuff' in the machine.

I'm sure others can chime in with some more experiences and knowledge.


Re: Suggestion to purchase of a high-resolution MS

Reply #2
Thank you, Corey.  They are exactly some comments I am looking for.