I would consider Orbitrap as the first option for the following reasons:

1: Excellent resolution

2: Possible to perform multiple levels of fragmentation (MSn)

3. Different modes of fragmentation (CID, HCD)

Hello Klara,

you write that you want to identify new compounds, i.e. you want to know the sum formula of the new compounds. This can only be done with an exact mass in combination with high resolution. A Q3 can therefore be ruled out. With a QTOF you are already in a range of mass accuracy of about 1-2 ppm and a resolution R = 30000 to 50000. Orbitraps have a mass accuracy in the sub-ppm range and are even better in resolution. Depending on your budget I would decide for a QTOF with a very good UPLC. In addition, you also need money for a maintenance contract or service and repairs. Orbitraps are much more expensive.

Regards Markus

P.S.: Concerning the service of Waters in Europe: Based on my experience in the last 20 years with Waters I can only tell you one thing: Don't believe everything you hear.

Thermo orbitrap and Waters/shimadzu qTof offer me similar price.

Hi Klara,

I've found this price list at the website of the state of New York. Maybe it will be helpful to you.

https://www.ogs.ny.gov/purchase/spg/pdfdocs/3870022962PL_Waters.pdf

Regards

Markus

Hi Klara

To solve your purpose QToF is the best solution

I recommend you two options -

1] Vion + H Class of Waters

2] LC of shimadzu compitable with A B S Sciex 4000 (More rugged instrument)

Please check the price and your budget.

Hello,

I would provide some useful references which might be helpful for your question about quantitative analysis with QToF and Orbitrap:

Article Simultaneous untargeted and targeted metabolomics profiling ...

Article A fast liquid chromatography-mass spectrometry (LC-MS) metho...

Article Large pesticide multiresidue screening method by liquid chro...

Regards,

Hikmat

Orbitrap offers much more powerful and flexibility in Ms/MS fragmentation than Q-TOF.

Markus Christ thanks for advice. Do you generally not recommend Waters, or just not everything is as beautiful as they say? Their representatives seem to me the most competent and helpful.

I have already spoken with representatives of all three companies and I know prices on the Polish market. QTOF with a good LC costs similar to Q Exactive Focus Orbitrap LC-MS. Both are within our budget.

thanks all.

I am less afraid of identifying new compounds because all 3 LC / MS have software specifically for pattern prediction and have numerous references.

I'm more afraid of routine analysis. I have heard that in qTOF I can't use normal patterns from Sigma, they must be radiolabelled. I do not really understand why. Is it true? Is Orbitrap the same? Before we buy the second equipment (probably Q3). I will do a lot of such analyzes. I will also need quantitative analyzes. But even in quality, I don't want to rely only on libraries, especially that in the case of LC / MS, libraries are less accurate. Previously, I worked on the old GC / MS (1Q) and always worked on the Sigma pattern in addition to spectrum.

Hi Klara,

we have several Waters LC/MS-systems as workhorses and they are not bad.

What can still be optimized is the Waters service: duration until a service technician is on site, quality of maintenance and repairs, etc. We now have our Waters LC systems serviced by Agilent and Providion is responsible for the Waters mass spectrometers. Since then we have been very satisfied with the quality of the maintenance. Salesmen always describe everything in very bright colors. Everything is great and works wonderfully. That is often not the truth. I would ask the sales representatives for reference addresses. The customers have practical experience and can tell you where the strengths and weaknesses lie.

Regards

Markus

Has anyone working on qTof or Orbitrap for quantitative analyzys?

I worked before on quantitative analysis of primary metabolites in plants using a Waters Xevo G2-S QToF (work published here : Article Simultaneous untargeted and targeted metabolomics profiling ...

P.S.: We have never worked on Isotope-labeled standard references. However, sure it will be necessary for absolute quantification in routine analysis.

Regards,

Hikmat

Orbitrap is excellent for quantitative analysis.

Hikmat Ghosson thanks. How would you rate the convenience of working on qTOF? Was he stable? How often did you perform the calibration?

Dear Klara,

Concerning the convenience of the Xevo G2-S QToF, I can say that the use of MassLynx and TargetLynx software (provided by Waters for targeted analysis) was relatively practical and can afford a good platform for routine analysis. Moreover, for the system stability, the reproducibility of the developed method mentioned above was validated after 6 months of the first application (data are shown in the article and the supplementary material).

Concerning the m/z calibration, we have done a “full” calibration each week using Formate clusters (and we should recalibrate each time we switch the ESI polarity), and it is an easy manipulation. Otherwise, the good advantage with the Xevo G2-S QToF is the real-time LockMass system, which calibrates m/z measurements during data acquisition. In all case, you need absolutely a stable temperature in the room where you want to install your spectrometer for a better stability.

It is worth to mention that the potential advantage of the ToF MS vs. Orbitrap MS in quantitative analysis is its higher scan rate. This can provide chromatograms that are more reliable. Personally, however, I did not worked yet on Orbitrap for quantitative analysis.

Good luck and best regards,

Hikmat

Have you looked at the Sciex QToF? They got good sensitivity similar to a triplequad instrument (Sciex 5500) and has excellent software for non-target compound (unknow in sample) by using software subtraction with blank of chromatogram. The issue of the Orbitrap is the trap itself. It will work with standard in solvent, but when you inject a real sample, matrix will fill up the trap and you will not see the analyte. They solved the problem by add a quad to the front to screen the parent mass and why they have Q-Exactive. However, if you are trying to screen 200+ pesticides, it will be tough and forget about the unknown where you don't know what mass to screen. Again, this is my experience only.

SCIEX qTOF is out of our budget. I dont need to skan 200+ substances or even 50+.

Hikmat Ghosson thanks. Someone who use Orbitrap tell me "Orbitrap is better, becouse we nee4d to the m/z calibration about 1-2 weeks, but in qTOF you must make it daily daily. But she don't use QTOF :P We know about temperature, but we will have good AC.

Do you have anyone in the lab with experience using one of the three brands you are looking at? Do you have anyone in the lab with QTOF or Orbitrap experience? How extensive is the customer support network for the companies you are talking to?

Learning an instrument from scratch is much more difficult than learning it with some sort of prior experience either in use of the software or the detector.

Waiting for a tech to show up can be an irritating experience.

We purchased a couple of instruments with little or no experience using that type of instrument and very poor onsite tech support. We regret it.

We don't work on QTOF or Orbitrap. I worked only with quadrupole (1Q and 3Q) and uv-HPLC, GC-FID. But I want to grow ;) Among my friends in the industry, no one has QTOF, but there are some of them in friendly universities. I worked on waters but only on HPLC. The service was helpful.

I have no experience with Thermo. I think I will choose Waters QTOF, because they have the most specialists in my country. In Thermo training will be in English, and in Waters in Polish. Waters also has technical assistance in Polish and only in difficult cases i will need English-language help. this is a significant difference for me, especially since I will learn a new technique.

Perhaps Orbitrap would be a bit better because it has a higher resolution and is more stable. But apart from the fact that he has an English-language service, it is also a bit more expensive (after negotiations about 25k euros). With such sums it's not like a lot but for a company to buy a hardware take is already a very large expense and these 25k can be outweighed.

I think the decision to go with Waters would be a good one. I assume you and your staff would prefer training and tech support to be in Polish. The fact that you are already familiar with Waters software is a good start.

ID of unknown coupounds will depend on Mass accuracy, Isotopic ratio fidelity; MS/MS mass accuracy and MS/MS Isotopic ratio fidelity. Ion moblity is a plus as more and more SW propose theorical ion mobility calculation and fitting but this is expending the price of the instrument. This performances are all related to the detector intraspectral dynamic range or to the number of ion counted in a single spectrum. Speed, Resolution and high intraspectral dynamic range in one single aquisition will determine the capacity to easily identify an Unknown coupound. Resolution is important espacially for complexe mixtures but can be overcome by UHPLC and Sample prep. Resolution between 80 k and 300 k are useless for that job as Isotopic ratios determination is perturbed by atomic resolution that start to appear and most of time pic picking and isoopic integration goes wrong for too high (or too low) resolution. Very high resolution only makes sense over 300-500 k resolution as atomic contribution can be clearly visible.

As Michael states, service in your area has to be a really important consideration. If you have a good relationship with the service team and you know several other labs who are happy with the service, then chances are you'll be happy with your purchase. Service engineers who are rather free with their time and consumables are a huge plus! Otherwise you can have the world's best MS, but if you spend most of your time getting high blood pressure trying to work out how to use it or waiting for service then it's not worth it.

Re qTOF vs Orbitrap: The practical difference between 30 000 and 70 000 resolution is not great, but 140 000 or 280 000 can make a difference for some applications. However for each jump in resolution, you'll lose scan rate, which will make a huge difference if you are doing high-throughput applications. So you may end up running your Orbi at 35 000 for most things anyway. They are good instruments and there are lots around. So for a clearly differentiating point, compare service.

Hi Klara

I am exactly in the same situation you were in last year. I am planning to buy LC-HRMS. Should I go for Q-TOF or Orbitrap? What you have purchased and what is the performance/satisfaction from your side

This thread has been very helpful. We in our organization are currently looking for an additional instrument. Fundamentally we do two types of works: 1. Lots of qunatitative studies involving small molecules and peptides for which we have a Sceix 3200 QTrap which has been serving us well. Then we have a Thermo Q Exactive HF-X Hybrid Quadrupole Orbitrap. Now the problem is that, we have a 5 years lease on the OPrbitrap which is ending and it has to be returned. There is no way to hold onto that instrument. We got a good offer from Shiumadzu LC-MS 9030 QTOF and I would like to know, if we can do quantitative proteomics study and small molecule analysis with this QTOF. On a nutshell, I would like to have experts opinion if having that QTOF can serve us both for small molecule analysis (MRM) and untargeted proteomics study.

Navid,

to answer the question on the quant proteomics studies, it would be necessary to know more details. Label-based or label-free? Which labels? E.g. TMT 10plex labels will only work on QEx systems, 6 plex or ITRAQ also works on QTOF's. I personally do not know the software from Shimadzu, but Bruker, Thermo, Waters and Sciex have good proteomics solutions for label-based as well as label-free approaches. So these are the ones I would look first for. Agilent IMHO is the budget choice.

For small molecule analysis, as previously mentioned, not only resolution is an important factor, but even more mass accuracy and isotopic fidelity. From my experience, in these two factors Bruker QTOF's are superior over Orbitraps (isotopic fidelity drops with increasing resolution) and Sciex QTOF's (mass accuracy not as good).

As mentioned earlier, QTOF's have to be calibrated much more often than Orbis. Not only daily but for important measurements I would recommend it in the beginning of the run. But this is not something to be afraid of, this can be done automatically and takes 20 sec. Here I see a clear advantage of the Bruker systems over the Sciex QTOF's. At Bruker you can inject the calibrant via a loop injection into the LC run and use this for calibration, in the Sciex software calibration on the TripleTOF's requires a separate LC run. Way more inconvenient and I have never understood why this was necessary.

Regarding MRM's: these can be done on a QTOF or Orbi, but nothing matches a QqQ here. The reason is the detector technology. QqQ work with electron multipliers, which have a much higher dynamic range (up to more than 5 orders of magnitude) than the MCP's used on QTOF's (typically up to 4 orders of magnitude) or the Orbis's, where the dynamic range is limited by space charge effects (usually 3.5 orders of magnitude intraspectral). Interspectral (dynamic range in LC run is not critical, that can be addressed by LC separation. Intraspectral dynamic range will limit your capabilities in detecting minor isotopic species or very low abundant fragments.

In Germany we have the term of an "egg-laying wool-milk-pig". Unfortunately it does not exist, nor does the mass spec which can address each task equally well. All technologies have their advantages and disadvantages which one should be aware of. If you know the limits of the systems/technologies, you can balance between the applications you need to run and define the best instrument. If not, you might end up buying the ideal box for label free proteomics but unfortunately that's not your main task...

Orbitrap with max quant should be the best choice but it is really dependent on what you are going to work specially on what PTM.

Hi Navid

Shimadzu's LCMS 9030 can do MRM quantitation for small molecules as well as for Biomolecules. Apart from this various analysis say aminoacids, vitamins etc which are quantified on a QQQ can be done on this Qtof. The mass accuracy is very good. I recommend going for Shimadzu. Should you need any more clarification feel free to write down I can address it.

It can also do your untargated proteomics also they support you with a database that fetches the m/z from library and you can zero down on the molecule of interest. do give this a try.

For unknown identification I would go with an Orbitrap - the resolution you quote is (70,000) is low. Current systems in the exactive range give up to 240,000 well beyond anything a QToF can do - these systems are also relatively easy to use. The Thermo focus is very high end and expensive and I think would be 'overkill' for you. Look at a Q Exactive or Q Exactive HF for the best resolution at the lowest price. Q Exactive also offers accurate mass of fragments in MS/MS so aids greatly in unknown identification

WJ. Wang, W. Chow, J. Wong, D. Leung, J. Chang, M. Li. Non-target data acquisition for target analysis (nDATA) of 845 pesticide residues in fruits and vegetables using UHPLC/ESI Q-Orbitrap. Anal. Bioanal. Chem. 2019, 411:1421-1431 DOI: 10.1007/s00216-019-01581-z.

I am very surprise to hear that people think more than 200 compounds screening or quantitation is hard on Orbitrap. We have had so many paper (validated method) published on QE. it can handle huge amount of target compound analysis in both quantitative or qualitative analysis. The same method above can use for vet drugs, mycotoxin, or we can call it a MVP (Mycotoxin, Vet drug, Pesticides) method . :-)

Depends on your budget and if you can afford than QE is your best bid, which can go over 140K mass resolution, or if the resolution is important to you then buy a QE-HF which can provide 240K resolution. Of course there are more Orbitrap machine in the family and can be very pricey.

Please feel free to contact me should you have any questions on Orbitrap family.

I guess this comment is late for the thread starter - I have the luxury of having both QTOF and Orbitrap in our lab and having experience with any type of sample, from cod liver, through blood, water to air. I would say it all depends on your budget. Q Exactive HF quoted earlier is a nice instrument but it is (at least in Norway) a lot more expensive than the top of the line QTOF. QTOFs have greater scanning speed and are not prone to overfilling the trap, so you will likely find more features in your metabolomics screening experiments. You do not run 240 thousand in a screening method (DIA/AIF) with a QE/QE+ (more affordable) because it is too slow..makes more sense with DDA..Ion mobility, for example, can be an option for you to help you with unresolved isobaric metabolites.. To this equation, please also add software capabilities and linearity range of different instruments.

It would be interesting what you got in the end.

The most misleading information on TOF is the scanning speed vs cycle time. The scanning speed may be impressive but not the cycle time . And also according to the guideline from Sante, Codex or FDA, the MS2 is for confirmation purpose and the quantification still based on the full scan then resolution is very important to separate the target compound and matrices. In order to speed up the cycle time and we are using 17.5 K resolution for DIA or DDA. Also using either variable windows or multiplexing to speed up the cycle time too. Typically, a full scan at 70 K and with 10 DIA windows at 17.5 K will take 1.2 second as the cycle time. In general an UHPLC peak is 12-15 seconds which can provide 10-14 scan cross the peak. If we do the apple to apple comparison by using 35 K resolution as TOF can do then it will cut the cycle time less than 1 second. Yes, Orbitrap is slow (QE HF can double the speed) , however if we can screening and quantifying more than thousand compounds in 12 minutes then it may not very slow at all. Regarding to software and it is a wash, all manufacturer can provided the similar software for the same purpose. However if you are in the unknown or method beyond the quantitation and screening then the Compound Discoverer 3.1 may be your best bet. My work is in the food safety area and my opinion only apply to the food safety analysis as well.