I am currently developing a LCMS method for certain genotoxic impurity in API on a shimadzu 9030 qTOF LCMS. And I had an argument with my coworker about which mode is more sensitive, SIM or MRM?
My coworker said that MRM is more sensitive based on his past experience using LCMS for API analysis.
I am relatively new to LCMS. But the way I see it, MRM is definitely more selective. But it is only more sensitive than SIM when there is background interference.
MRM is a MS/MS method, which should have fewer ions compared to SIM, which is a MS method. So if we have a clean standard or a sample which has no signal at this particular m/z around the retention time of the target, SIM should be the more sensitive one.
Am I wrong?
Thanks in advance for any comments!
Theoretically, the SIM method could obtain higher abundance peaks due to not losing the ions in the process of MRM transition. For instance, for higher m/z ions SIM could have high abundance with a relatively low noise signal. However, the MS/MS mode has advantages that should lead to MRM usage (noise reduction with the simultaneous confirmation of compound).
Sometimes the use of SIM is the only option. Some sterols-related compounds when using fragmentation give a very characteristic fragmentation pattern with no predominant ions.
SIM for better sensitivity, MRM for better selectivity.
There is always a trade-off, thus it depends on your needs/ expectations, your sample composition, and your applied sample prep workflow. Much information is needed to accurately suggest the proper mode of acquisition.
As Dr. Zymslowski points out it is compound dependent. One of the best ways to "enhance" signal is to lower the background noise, which MRM does quite efficiently. You have noise in single quad mode no matter what you do, so in practice if you have viable parent->daughter transitions you normally have more apparent sensitivity using MRM than you do with SIM. There are cases where SIM is significantly more sensitive than MRM because you don't have any significant collision-activated dissociation occurring. I tend to view them as complementary analytical modes since the amount and type of quality assurance required to generate adequate data changes for each mode.
As Dr. Zymslowski points out it is compound dependent. One of the best ways to "enhance" signal is to lower the background noise, which MRM does quite efficiently. You have noise in single quad mode no matter what you do, so in practice if you have viable parent->daughter transitions you normally have more apparent sensitivity using MRM than you do with SIM. There are cases where SIM is significantly more sensitive than MRM because you don't have any significant collision-activated dissociation occurring. I tend to view them as complementary analytical modes since the amount and type of quality assurance required to generate adequate data changes for each mode.
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