Yes, the full scan instrument these days has good enough sensitivity to replace the Quad instrument and can do more , particularly non target and retroactive review.

Quad instrument has a limited number of pesticide that you can scan but full scan instrument has unnlimitrd number and you can see some unknown analytess in a later date.

Hello Sherif, I don't have any experience with LC/MS/MS now, but I know the Agilent and Waters TOF systems. If you choose a TOF system, take one from Agilent and not from Waters. Waters still uses an outdated TDC (Time to digital converter) technology as opposed to Agilent. This has two negative consequences: 1. Determination of the exact mass only possible in the peak edge. 2. Small linear range (detector quickly enters the saturation range). My recommendation: Agilent TOF 6230 (or later). In routine operation mass accuracy at 2-3 ppm, very good measurement of isotope peak patterns, fast scan rate (40 Hz), mass resolution R = 10.000. Thus coupling with UPLC is possible. Cycle time in routine operation 1min per sample. In combination with a 50 mm column (ID = 2.1 mm) a peak width at the baseline of 0.5s is achievable. This means that you can resolve up to 50 peaks within a chromatographic run time of 30s. To get you started, I recommend the book by Imma Ferrer and E. Michael Thurman' Liquid Chromatography Time-of-Flight Mass Spectrometry - Principles, Tools and Applications for Accurate Mass Analysis' (Wiley, 2009). Greetings Markus

thanks for your discussion dr Narong

 thanks markus for your helpful discussion and advice

Collecting data is one thing, interpreting is another thing. You will need a smart software to help you identify the unknown. I am kind of Sciex guy and like their software. Waters has a good one as well. One problem of Thermo is their instrument is ion-trap and matrix will fill the trap so you would not see the analyte. I would think twice if you want the Thermo version of accurate mass machine.

thanks, dr narong, I really prefer absciex and bruker, based on reading related articles and available specifications. Absciex is more familiar with me since I have a good experience with its LC MS/MS instruments and I think that the trouble shooting will be the same for the LC MS TOF (mainly at the ESI).

My question is : if you will buy an instrument for a new lab, will you buy LC MS TOF or you will not take this step and make the first instrument LC MSMS and may the next will be LC MS TOF, and which you prefer Bruker or ABsciex

thank you

In my lab, we don't have much choice of choosing LC that come with MS. I usually have Shimadzu pump which has very low carry over, but it comes with two high pressure pumps so y cannot pump solvent more than two at a time. You can buy a solvent selector add-on so you can do a1 and b1 or a2 and b2 (it is high pressure mixing mode). If you have Agilent pump, it comes with four solvent but can do two solvent at a time.

The quad instrument has a limited use because it has a limited number of analytes you can scan. The non-target analysis is a new trend right now and since the Q-ToF is as sensitive as 5500 Sciex, I would buy only one instrument. The most benefit is that you can look at the data you did  a month ago and search for something that you were not looking at the time.

thanks dr narong for your useful discussion.

For the used lc, It prefered UPLC one especially when using Ms tof technique. Using Uplc system will enable the usage of the fast mrm, scan,  and different  abilities for Ms Tof. 

thank you

That is depending upon how fast is your scan rate. I remember 7 years ago, we have API-4000 with UPLC column to shorten the run time. However, the scan speed is not fast enough to scan 500 MRM (250 analytes) and I have to lengthen the run to make the peak wider and use a regular LC so I have at least 10 data points/peak

Ion trap technology has matured from the early days, 10-20 years ago. Everyone interested back then had these issues. But modern Orbi-traps do not have this problem. 

An ion trap and orbi-trap does fill up with ions if unregulated as they used to in the past and the result would be secondary ionization which made quantitation difficult but interestingly not qualitative.

In the case of the modern Orbitrap, there is a regulator called the Automatic Gain control which regulates the amount of ions entering the orbitrap to avoid secondary ionization. You can set it automatically or manually to avoid any issues.

Thus, because the ions entering the orbi-trap are below capacity, there are no issues and you get increased resolution and accuracy and due to the design of the orbi-trap can go from 17.5 to 280k resolution.

I have been performing pesticide analyses for over 40 years. Most of it related to new compound registrations under GLP protocol. LC tandem mass spec is still the way to go. The new challenges for modern pesticides are ever increasing need for sensitivity and specificity. THermo has many options including  orbitrap for the final detector. Being used more and more for complex and difficult analyses. The trap allows for unprecedented mass resolution (>200,000). Price has come down as well. . Sensitivity on these systems is getting better  and with robotics, in-line extraction extremely efficient. We had a fully automated system with robotics and the throughput was unbelievable. Little down time despite many valves.

thanks a lot, all of your answers support using new high resolution mass technique. Now, we discuss the efficiency of orbitrap vs tof. and tof (LC MS TOF) for ab sciex and bruker. Isnt it?

If one have a document (Research article, application note, ...) that explore addetional or unique advantges, properties of his openion about orbitrab, Lc Ms tof for a specific company please attach it, or just rrefer to its title

Thanks for your support

Enter your ansIwer

Thank you Sherif. Will post some useful resources in a bit.

Dear Sherif, we are currently planning to buy a Q-ToF, however it will not be replacing but complementing the tripple quads. I agree if the job is a quantitation job the tripples are still the way to go.

If You have money for one instrument and you need to do both quantitation and structures etc, the Q-Tof might be the way to go. Into my perception the Q-Tofs have acieved quite a bit in respect to sensitivity and linearity in comparison were they were 10 years ago.

Hi Sherif,

Here are some resources for looking at high res platforms in general and Orbitrap users experiences, links attached:

-Biocompare 2012: Getting to the Right Answer with High-Resolution Mass Spectrometry

-Can Your Q-TOF...Keep Pace with Your Needs?

-The Switch Is on: from triple quadrupoles and Q-TOF to Orbitrap High Resolution Mass Spectrometry

http://www.biocompare.com/Editorial-Articles/113434-Getting-to-the-Right-Answer-with-High-Resolution-Mass-Spectrometry/

https://www.thermofisher.com/us/en/home/products-and-services/promotions/industrial/buy-hram-orbitrap.html

https://tools.thermofisher.com/content/sfs/brochures/WP-64911-MS-Orbitrap-WP64911-EN.pdf

Looking at the discussion above I see a comprise between structural elucidation and quantitative analysis when Orbitraps are compared to QTOFs.  is it the interplay between  resolution vs sensistivity? but why? What is the technical  limitation for an orbitrap not  being as fit as Q-tofs for a quantitative study? Is that the gain on ions being limited in orbitap? Is there really a big gap between Q-tof and Orbitraps?

Firstly, to address the original inquiry..... it is very practical for modern TOF MS to perform pesticide analysis previously only possible on TQ's. The main reason for this is that during the time it takes for regulations based on TQ's to be implemented development on TOF's advanced in leaps an bounds. This has lead to modern QTofs with sensitivity equal to or better than the TQ's used to develop multi residue pesticide methods. Of course, TQ development also advanced across the same period so the advantage of the TOF is not so much limited to the speed (for long lists of pesticides) since TQ's are very fast these days as well. The sensitivity and specificity of the HRMS TOF data combined with it's ability to elucidate the structure of unknown pesticide formulation components and transformation products or non-pesticide related contaminants are the reasons TOF is steadily increasing in use for pesticide screening across time.

Secondly, I'd like to address a few clarifications worth mention based on earlier comments. The use of TDC's in the detection systems of TOF's, once the state-of-the-art, has been replaced by the use of hybrid detectors and ADC's in all current TOF MS from Waters Corporation. In fact this has been true for the past 8-10 years now, so the earlier comment about TDCs and their limitations is irrelevant to the original question of whether or not TOF can now replace TQ for screening. For the real extracted samples encountered in pesticide screening, quantitative linear dynamic range is comparable between TOF and TQ. Dynamic range for accurate mass measurement is also improved with current generation TOF detection. Furthermore, trapping based HRMS used in screening typically acquire data in the 15,000 to 70,000 FWHM resolving power range within a screening experiment. Numbers of 200,000 and greater for FWHM RP are only achievable outside the context of screening experiments and so are not strictly speaking responsive or relevant to this inquiry.

Finally, it's worth mentioning the importance of data processing in screening work. Hardware specifications and performance aside, labs considering migrating to an HRMS screening approach for pesticides should be prepared to perform a detailed evaluation of the software capabilities. This is critical due to the density of information available in each analysis. Extracting the full value from the data and reporting it effectively is important and somewhat different than the processing and reporting requirements for targets-only TQ approaches. In the end hardware and software "fitness-for-purpose" are important to each approach.

If you wanted to see a comparison of Tof Vs Trap for contaminant screening the only datapoint I can think of is a poster by the FDA (G Mercer, R Self and W Cooke) which was presented at NACRW, St Pete’s Beach, FL, USA in 2015. It compared the results and data review of well characterized samples from LCMSMS on a Waters LC-Tof with UNIFI Software to a Thermo QE.

Thank you for your question. It has certainly raised some excellent discussion and is very timely given the continuously increasing use of HRMS screening for the analysis of pesticides.

Enter your answer The suggestion was to use triple quad and the addition of an orbitrap instead of a quadrupole detector was a suggestion because of the superior mass resolution of the daughter ions.  A QTOF cannot do the experiments a triple quad can, example product ion scanning, precursor ion scanning, constant neutral loss scanning and single/multiple reaction monitoring. These tools are important especially in light of the new wave of pesticides and the difficult matrices involved in testing. Its a balance between sensitivity and specificity and my personal experience suggests the triple quad is a better option.. The earlier versions of Q-TOP had issues with quantitation I do not know if those have been resolved especially in the pictogram range.  Due to risk assessment limits for pesticides, especially in foods, are going down not up

Let me add, I concur with the approach in contaminant screening of having sufficient triple quad capability prior to investing in a HRMS system. 

The high resolution and mass accuracy of TOF can increase the specificity and partially compensate for the loss of specificity by using a single stage of MS rather than two stages of MS. However, one weakness in this approach is that TOF cannot separate isomers, so you will need to rely on the LC to separate isomers.

Also, there might be some isobars that are difficult to separate using TOF MS alone. When I say "isobar" I mean compounds with the same molecular weight be different molecular formula. Isotopic distribution differences can sometimes help distinguish isobars, and of course the accurate mass can sometimes distinguish isobars as well.

There are many instruments out there and instrument manufacturers and their sales support are experts without question. However, having worked for government and a public company my experience is that funds are hard to come buy. You cannot afford to buy the wrong instrument. If you do your carerer could be jeopardized.  Ask yourself why you are buuying an instrument? What do you plan to do with it both in the present and the future? Send extracts of samples which have been spiked (or are known to be contaminated) and cleaned up for the  analytes and matrices of interest.  All instrument manufacturers will be more than glad to analyze and show what they can do. Do not forget the data system, not all are equal. . We almost lost $0.5M client because we employed a trap instrument (not orbitrap) many  years ago to attain increased sensitivity for a large monitoring program utilizing fish bile. It was a disaster because data did not fit with conventional quadrupole because traps dump ions when full. Sample analyses are critical to making an informed decision.