urgent help regarding the most sensetive LC-MS/MS system

[clinicalpklab]

Hope you are all well.

I am in the position of purchasing a new mass spect system but want to buy a system with the best sensitivity for use in a research environment with clinical application (not GLP though). This is to be able to measure the concentration of free drug which is much less than blood level.

The choices in my price range are:
(1) Thermo Quantum Ultra with UPLC from Thermo (Demo mass detector, new UPLC)
(2) Xevo™ TQ MS with Waters ACQUITY UPLC MS/MS (Demo for both)
(3) ABI 4000 with Shimadzu Prominence HPLC (new for both)
(4) Shimadzu Nexera with LC-MS-83 (new for both)

Which one of these systems would you recommend (i) in terms of sensitivity (ii) in terms of ruggedness, ease of use and overall performance.

Any advice will be greatly appriciated.

[Gaetan Glauser]

I will answer what any sensible and disinterested person would: you should ask for a demo on the 4 instruments with representative samples. Then also take into account other aspects than sensitivity such as easy-of-use, aftersale service in your region etc. If your instrument is ultra-sensitive but does not work, you won't make much progress. There have been a lot of talks on that subject and the conclusion is always the same: you can't get an objective and definite answer on such topic.

[JGK]

I will answer what any sensible and disinterested person would: you should ask for a demo on the 4 instruments with representative samples. Then also take into account other aspects than sensitivity such as easy-of-use, aftersale service in your region etc. If your instrument is ultra-sensitive but does not work, you won't make much progress. There have been a lot of talks on that subject and the conclusion is always the same: you can't get an objective and definite answer on such topic.

This is the way to go, but I would add that:

1. You should specify the method being demonstrated;
2. The instrument setup should be done in your presence and not in advance;
3. You provide the column and the samples. If possible use the same samples & column for all demo's.

This will give you the most information for a true comparison.

Plus, LC-MS-MS sensitivity is dependent on the compound being assayed it's not the same for evertything.

[Gaetan Glauser]

Entirely agree with JGK, I made it a bit short because of all previous posts on that topic. About the method to be specified: this means the chromatographic method (same column, same gradient, same additives and same injection volume), and same transitions in MRM mode (if you determined them). This will enable you to compare chromatographic systems at the same time.

Never send samples and wait for results, otherwise you will test the honesty of manufacturers and not the sensitivity of their instruments!

[lmh]

I'd like to add one proviso to the previous postings. As well as making the manufacturers follow your method, it's probably a good idea to let them additionally have a go doing whatever they think will give the best results.

The reason is that their instrument may offer some unique feature that will give you vastly better results. For example, if you test all your manufacturers with a lowest-common-denominator hplc method, you won't see that one manufacturer can offer a superbly optimised UPLC approach with vast benefits. You may, indeed, ultimately want to choose an instrument because it is capable of something its competitors simply cannot do.

Of course there are a few dangers. If you are using a formal tender process you will have to make sure you can still assess the results fairly, and balance the compulsory and optional data (what do you do if manufacturer A has the least sensitive data using your method, but the most sensitive in the freestyle measurements?). You also need to be sure you are testing the instrument and not the demo chemist's ingenuity!

On another note, I have to say I have never come across blatant cheating by manufacturers. The risk isn't that they'll lie, the risk is that if you leave any freedom, they will obviously exploit it to give the best result. For example, if you are looking at quadrupole instruments, and indicate you want high sensitivity, don't be surprised if a manufacturer sacrifices mass resolution (and hence to some extent specificity) to boost sensitivity.

[giacomo56]

You missed the ABI 5000, 5500, 5600 and the
Agilent 6430, 6460 and 6490 units....

IF you want sensitivity.....or, are you purchasing based on price? Or what they want to sell you........

[yangz00g]

With all due respect, I don't 100% agree with the recommendation of a demo as only way to go, except that you know the demo compounds are the only compounds to be analyzed on the instrument. In real world, you won't know what your next analytes will be.

So is there any standard way (or kind of) to compare the sensitivity of instruments without a real demo? Yes, the S/N (and how to calculate S/N) ratio of Reserpine. You may find information of it from most instruments and use it as a baseline for comparison. And then, a demo may make your choice easier.

As giacomo56 mentioned, you missed the top QQQ performers like API5000 and Agilent 6490.

[Gaetan Glauser]

Except if reserpine is your next analyte to quantify, I cannot agree.

Here is part of a previous post that "lmh" wrote:

"Each company defines things slightly differently, making the data very hard to compare. For example, most will publish sensitivity using reserpine, but each will report different S/N on different size injections and it takes some ingenuity to put them on a comparable basis. Even S/N can be defined in different ways. If you get your own test data, you can make sure it's comparable".

When you are about to spend half a million dollars for a machine, you can afford to ask for a demo and be present on site.

[CE Instruments]

You missed us off
Sensitivity is matrix dependent and also dependent on other compounds of interest. Triples are great if you only want to see one compound but it can be handy to see what else is there. Is it just target analysis ? Quantitative sensitivity level ? Could high resolution help resolve interferences ?
Please add Bruker to your evaluation list
As posted above.
Define your requirements, decide on a budget, submit a method and samples, evaluate the data, try the software for ease of use. This should help you pick the right system.

[hermo71]

Maybe clinicalpklab has a limited budget if he missed Agilent 6490 and AB Sciex 5500, otherwise he would have asked for a TSQ Vantage and a Xevo TQ-S instead of a demo TSQ Quantum Ultra ans a demo Xevo TQ MS? Don't you think so?

Go with a demo with your real sample and you'll discover which instrument is the best for your purpose.

[giacomo56]

it's the battle of the sales reps...on this thread....

Buy what you want...demo it....like it...run it....get your work done. Asking a question like that here, is asking for a thousand opinions and all from a "company man"

Tell you what I did in order to buy an instrument...get a list of 10 users and call one at random, see which company gives you a list, it will ween out the ones that are really not that great.....

[hermo71]

Yes Giacomo56...you forgot to say that you are an Agilent man..)

[giacomo56]

Where would my posts be a biased one....I mentioned both Agilent and the "ABI" instruments to be fair to all, that were missed in the evaluation; and I never expounded the benefits of the A product..have I ?

This is NOT a forum to push a single vendor, but better science done by all. Sure they are biased opinions everywhere on this forum....I don't need to voice of the obvious.