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Dear All,
I am working on a molecule with very less response, so i had to change my Resolution from High to low in mass spectrometer, Now i want to know that whether FDA or any regulatory agency have objection for data generated with low resolution in mass spec?
Kindly respond
Thanks in Advance
Jacob
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The following message was posted to: PharmPK
Dear Jacob,
Ultimately, the validation of your new settings should speak for themselves. If you can show that e.g. specificity and/or interference by co-medication and metabolites is not negatively affected by your low resolution settings, it should not be a problem.
Good luck, Jan
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You need to demonstrate selectivity during validation. If you have demonstrated that the best response is with low res, and you validated that way and your selectivity requirements were met in validation you should be on solid ground. You should be able to provide evidence that you tried high and unit resolution.
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The following message was posted to: PharmPK
Dear Jacob,
Resolution selection is never discussed in any regulatory guidelines. As
others suggested, as long as you validate your method using same
resolution, you can use it.
However, I am just curious to know, why you are not getting good
sensitivity using unit resolution , and how much sensitivity improvement
you got by using low resolution. (I guess, the sensitivity gained is not
worth to risk losing specificity of MRM or SIM detection.
Regards,
Vinayak
Vinayak Nadiger
Manager, Bioanalytical
Forma Therapeutics(Singapore)
11,Biopolis Way ,Helios # 08-05
Singapore 1386607
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The following message was posted to: PharmPK
Dear Jacob,
As others pointed out, as long as you validate your method to show it performs correctly using a resolution rather than another is not a problem.
"High" and "low" resolution are actually not very specific definitions of resolution and may encompass different conditions. Did you try "unit" resolution (for quadrupole this is usually defined as 0.7 amu full width at half maximum FWHM for a singly charged ion)? Some makes of instruments work routinely at very high resolution, so unit resolution may be considered "low" for those.
When using a triple quadrupole different settings may be used for Q1 and Q3, so you could use a lower resolution in one quadrupole to get more signal, but still keep it unitary or high in the other, so as to keep some specificity. In my experience trial and error is the best guide in finding the most suitable settings.
Another thing to keep in mind is how the instrument's software establishes "high" and "low" resolution. In some makes of instrument "low" resolution in particular is not calibrated to a specific FWHM over the whole range, instead an "arbitrarily" chosen value (e.g. drop offset) is taken of the resolution table. The choice of this value will cause more or less widening of the mass peak at any m/z, as the same value is subtracted from the entire resolution table the widening is not the same over the entire m/z range. If this is what your machine software does, it may be worth for you to check how wide your peak really is in "low" resolution (how low is "low"); this information may also be useful if you change instrument, or analyse samples on different instruments(of the same model), as resolution tables and drop-offsets can be different between instruments you may have some surprises using low resolution settings in different instruments.
Patrice
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