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The following message was posted to: PharmPK
Dear group,
If you already have a 3200 QTrap in your lab, and plan to purchase the
2nd mass spec, a higher level one (higher than 3200 Qtrap) for the
application of metabolite analysis, clinical samples for PK, and
formulation development work. What instrumental model/vendor would be
in your mind (ABI, Thermo, Agilent, Waters, Bruker, some venders I
listed here for example)? Money is an issue but not be restricted very
much, say in a range of 300K to 600K?
Any insight or opinions would be appreciated.
Thanks a lot,
Steven
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Dear Friend,
The query is very broad, moreover the intended application of the Mass
Spec.
Qtrap 3200 holds good only for the quantitation work and feeble type
of the identification work if you wish to og upto MS3, but at the same
time it may have the limitation on the side of the mass range you
prefer or the LOQ of the system.
It is very rare, even impossible to get the best Mass Spec instrument
that serves as all in one for all of your desired applications.
What I understand is for the preformulation works such as the LogP,
solubility, intrinsic metabolic stability analyses and forced
degradation samples analyses (if you do not desire characterization),
plasam protein binding analysis and the high throughput solubility
experiments you can go for the better versions of the API series, AB
SCIEX Triple Quad(TM) 5500 (check price may not fit in your range),
being the best claimed one, this would hold best for your clinical PK
sample analyses also.
The step ahead is metabolite analysis where you need to have both the
power of the quantification and the characterization, where Q-TOF
holds the best one (they are even provided with the nanoESI ionizaiton
modules also, that increases the sensitivity of the system). Though,
you can do upto MS2 with this instruments, due to its immense power of
the mass acuracy and resolution, you can perform HRMS the best, plus
the availability of the ISCID like options help to get rid of the
matrices. So, to some extend this Mass Spec suits your desire the best.
The best of the today I will suggest is the LIT-Orbitrap (I am not
sure of the price), it is 2 D trap with the promising trapping
efficiency, power of comparable HRMS as TOF instruments, and the best
part is MSn upto n=10 (n>6) practically. At the same time you can also
use it in the TQD modes. So, it is the best one that serves ofr the
best characterization purposes, where you can work for the structural
charactrization of the drug-drug, drug-excipient interaction products,
degradation products in the formulation, metabolite identification
with the Hydrogen/deuterium online exchange probe in additon.
Concerned to Vendors, as most of us are aware of, never rely on the
HPLCs only:
1. For TOF based instruments Bruker Daltonics are pioneer
2. For TQD instruments, API are the best ones
3. For Ion traps, non are comparable ot those of thermos
4. For the dual multi-mode ionizaiton sources (+/-, ESI/APCI),
Agilent are the best ones
Rest Q-TOF, equally good of Agilent and Waters, though Brukers are the
best ones, Single Qauds Agilent are the best group.
Hope, this may help you!!
Regards,
Amrit
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The following message was posted to: PharmPK
Most labs in a regulated environment fall under GXPs. Part of the GXP
will focus on validation master plans and instrument validations.
Instrument validations require formulation and formalization of needs
presented in a user requirment specification or USR
You and the others in your lab need to list what you want this new
instrument to do, sensitivity, selectivity, ability to use N2, He, Ar,
ability to use photo, electro spray, etc. Require a min cycle time for
scans and ability to change from pos to neg during a run, use ion
trap, etc, etc.
Your purchase should reflect what you want the instrument to do.
On the practical side, software validation and training will be
simpler if you stay with the present vendor but if your needs (above)
suggest otherwise, you will need to go to another vendor.
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Hi Steven,
What will be your major application? If Metabolite identification is not
a major activity, I suggest you do not need to have another trap in the
Lab. Either a top end Triple quad or QTof would be a good choice.
I would choose a vendor based on following sequence:
Compare list price of equivalent models.
Evaluate the performance of machine practically. Do not get carried away
by sales talks.
(Choose a least sensitive analyte that you have analysed on Qtrap
3200.Get it analysed by all shortlisted vendor machines. That would
straight away tell you how much more sensitivity you are going to
achieve by shelling out more money.)
If the service back up is best for second best sensitive machine, I
would rather go with it.
Regards,
Vinayak
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Hi Steven,
I dont know the answer of your question, but i need to know your
experience about quantitative analysis in Q Trap 3200, is it good
enough for quantitative analysis
With regards
Sagnik
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Our lab has been successfully using Thermo Quantum ultra. It has very
high signal to noice ratio. which i have hardly seen in 4000. I donno
why thermo has not claimed such good s/ n
We measure 0.1 ng/ ml on column in plasma easily
At lloq our S/n is above 50
Easy to clean no need to vent for cleaning and good service in most
countries
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The following message was posted to: PharmPK
Hi Amrit,
Thank you very much for your input.
I agree with you that it is impossible to get the best Mass Spec
instrument that serves as all in one for all of your desired
applications. The next instrument I want to have is for metabolite ID
mainly, if not at all. A sales person talked to me about 5500QTrap,
which is claimed as the instrument of NEXT generation. The selling
part is its scan speed and sensitivity.
I would agree with this sales person at that the scan speed is
sometime more important than sensitivity. For example, a peak of a few
second in a LC run, slow scan instrument cannot proved useful
information. What do yo think?
LIT-Orbitrap is a good one, but the price is not good.
Again, thank you very much for your insight.
Steven
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The following message was posted to: PharmPK
Hi Vinayak,
Metabolite ID would be major task for the next instrument. The
suggestion is appreciated.
Thank you.
Steven
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Hi Sagnik,
Is it for small molecule? what is your expection for detect limit?
What is your budget? I cannot answer it without knowing this.
Regards,
Steven
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Hi,
How about metabolite ID work on this instrument?
Thanks a lot.
Steven
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The following message was posted to: PharmPK
That is then one of the features to add to your USR- I indicated it as
cycle
time. The other advantage is that is would use analyst software
which you
have on your 3200 so that the validation and learning curve would be
shallow.
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Hi Steven,
Yes, it will be for small molecules detection; quantification will be
its primary purpose, if we get met ID info, then its an added advantage.
With regards
Sagnik
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Hi,
It's been interesting to look at your considerations. I have an API
3200 QTrap, an API4000 and a Brucker (Agilent) ion trap in my lab. We
use them somewhat differently according to the target analysis (we do
tissue residues and PK).
You can find excellent instruments from all the major vendors.
Basically the papallel models will do more or less the same things.
Naturally everybody will say why theirs is the best, but that's part
of the game. However, when you do an investment of this size, even the
small things may matter. Based on the characterization of the problem
(target analysis) here, I would probably look at Orbitrap, which
unfortunately is extremely expensive, or it's considerably cheaper,
but not cheap, little brother (forgot the trade name, sorry). But
maybe I didn't understand the prospective application correctly.
Rarely is the sensitivity a problem, but when it is, it may be
compound specific. Surprisingly, this compound specificity seems to be
sometimes linked to instrument specificity. So there are no simple
answers to certain questions. Good service and support are very
valuable and must be taken into a consideration.
You can learn a lot from the specs, but unfortunately they are not
always comparable. It would be great if the vendors would agree on, at
least, a basic specs panel (including units). I must admit that I have
a great weakness for the ABI Sciex ion source and I don't think it is
purely emotional. It is simply a work of art. It had a lot of
influence on my purchase decisions.
Anyway, good luck!
Stefan Soback, DVM, PhD
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The following message was posted to: PharmPK
Hi Stefan,
I agree with your comment. We compared 3 suppliers with actual samples
analysed on their machines by our senior technician on site.
We settled with Agilent 6410 QQQ and now have added newer model 6460
QQQ with better sensitivity (again a function of chemical class I
would say). In terms of software MassHunter is much easier to learn
and is very user friendly like Agilent Chemstation to control HPLC. I
am not saying others are too difficult, but surely depends on
individual capability to learn.
The one big advantage, Agilent 6410 QQQ has a multimode source (world
first), where you can individually and simultaneously use EC and APCI
without having to worry about changing the source. Dual source along
with multimode engineering design can be exploited to its full
potential with experience Waters too have come up with a multimode
source recently.
Only disadvantage I would say is the lack of capability to do the
automatic method optimisation but again it is not that tedious to do
manually. Automatic optimization would save time in a very busy lab
with a simple tweaking from an operator. As far as I know Agilent is
working on it and soon would be a standard or integrated to existing
system.
As far as service and support is concern, we never had any problem
despite sitting at the end of the world (New Zealand). Again it is
very important criteria for selection.
IMHO a lab should talk to the different vendors about their needs and
ask them to test their set of compounds. Simply shouldn't be carried
away by their specs. Based on the results, they should decide which
one to go for. Remember it is substantial investment in any lab.
Cheers,
J
(above is purely my opinion)
Jagdish Jaiswal, PhD
ADME Pharmacologist (Research Fellow)
Auckland Cancer Research Centre
University of Auckland
Auckland
New Zealand
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Hi Jagdish,
Thanks for your comments. Yes, Agilent is a wonderful instrument. In
my lab all the LC, GC and GC/MS instruments are Agilent. We have
surprisingly little use for APCI and it is very easily changed in the
Turbo V interface (but cannot be used simultaneously).
Going back to the original problem Steve presented (i.e. metabolite
identification), triple quad instruments are not optimal. The API 3200
linear trap obviously gives additional significant possibilities
compared to an ordinary triple quad. Going for the API 5500 QTrap
would probably only increase the sensitivity and other operational
features (if you have the clean facilities for operating it), but with
no real additional information. So I don't see how you could really go
much beyond the API3200 QTrap capability this way. But again, if
sensitivity is the issue, go for the 5500 QTrap.
To add new dimensions to metabolite identification, the Orbitrap or
Exactive (the little brother), with ppm range mass accuracy, appear
most useful for the problem. Now you can look at your potential
metabolites from a totally new angle, especially if you have to ID
them. TOFs would probably also do the work, but you loose some of your
confirmative power. I also have a feeling that the sensitivity of a
TOF is still inferior to Orbitrap/Exactive. This, however, is purely a
guess, because I don't have any experience with them, not to speak
about comparisons.
Very best,
Stefan
Stefan Soback, DVM, PhD
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