Use MS1 or MS2 for a SIM-Method on Agilent 7010 QQQ ?

Question

We want to validate a SIM-Method on an Agilent 7010 QQQ. Which MS should we use for that?

paulsalverda · Accepted Answer

SIM works on a QQQ, yet there are nuances on how to run it as the system design is optimized for MRM. There are possible benefits to both ways. Are you only doing SIM on this 7010 for this method? Will you be doing SIM/Scan, ? 
 MS1 SIM - the first quad is simming the ion list, the collision cell still has the gases flowing, and the second quad is passing all ions. 
 MS2 SIM - the first quad is passing all ions, the collision cell still has the gases flowing, and the second quad is simming the ion list. 
 The collision cell gases must be on since they need to be on to get a valid autotune and if they are turned off after the tune - the system changes and the tune values are not all still valid. The changes affect all that happens in and past the collision cell. Ion focusing, ion energy - speed, if you will, removal of metastables to reduce noise...the collision cell function is important and the gases at the correct flows, the same flows as used in tuning, are critical for best performance. 
 There are ion losses as each quadrupole works, even for the ions of interest. There may be better sensitivity using MS1 as simming is throwing away all other ions right away, so there could be less ion/ion interference down Q1-CC-Q2. There may be better sensitivity using MS2 as MS1 has passed all ions (that it can, at least) through to the collision cell where some losses occur, and then MS2 throws away all the other ions there. The mass assignments may be slightly better one versus the other - but what I've seen they're both totally fine. The ion ratios may be slightly better one versus the other - but what I've seen they're both totally fine - - as long as you don't have peaks that are too big. 
 Let's talk about more than that choice, though. The 7010's HES puts out 20x more ions than the orthogonal ion sources (SS/Inert/Extractor). Too many ions crashing on the front of a quad can damage the quad itself. In SIM, like MRM, you are using the quad to filter out all the ions that are not specifically the ones of interest. All of those other ions either crash into the quad or go between the poles and eventually bounce around inside where they finally bounce into the high vacuum pump. It is important that you know how much of this is going on by running samples in matrix, like your highest standard or highest samples, in MS1 SCAN mode. Reduce your concentration, reduce your sample injection volume, or increase your split ratio so that the Scan ion signal never saturates.

1. Run each new sample extracts in full scan mode (ie MS1Scan) with EM gain set to ~0.5. 
 If any of the peaks in the chromatogram are flat topping (ie overloading the detector) please do one or more combinations of the following: 
 a. Inject less until the chromatogram comes on scale. 
 b. Run the sample in split mode (use ultra-inert split liners) 
 c. Dilute the sample 
 d. Do further sample clean up 
 2. Make sure column flow rate is <1.4 mL/min into the MS while the filaments are on 
 3. Always run constant flow methods 
 4. Make sure the solvent delay is cutting out all the solvent 
 5. If using CFT (backflush or splitter plate) ensure there are no leaks. 
 6. Always make sure the quad temps are not >150C 
 7. Only certain applications need a source temperature >280C, so use 280C as a maximum temperature for the source when running samples.

And since you're reading - clean the source sooner and more often. It's easier to clean a barely dirty source than to have to work hard at cleaning a filthy one.

paulsalverda · Answer

Notice I didn't really answer ;) Yeah, you would really need to do very detailed experiments to prove that one way or the other way is actually better for your peaks of interest since chemistry is involved at all steps. That collision cell complicates things - for the better, of course. That is such an annoying answer to type, though. I recommend MS1 SIM and MS2 Scan - as theoretically there is slightly better sensitivity in MS1 SIM and slightly better mass assignment in MS2 Scan. 
 
 SIM/SCAN is a really helpful tool. You may not need to run all of your samples or methods that way, but it lets you see the bigger picture in Scan while still seeing the details in SIM. 
 Try not to have too many SIM ions per cycle and not too short or too long a dwell time per ion which depends on the number of ions per cycle. Find the balance of number of ions and dwell time to get you enough SiM ion cycles per second to give you enough data points per peak to get you good quantitation.

Use MS1 or MS2 for a SIM-Method on Agilent 7010 QQQ ?

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