Linearity in GC/MS/MS analysis for Mutagen X using ion trap

[julescarlson]

Hello,

I am working on an analysis for Mutagen X (MX) and Mucochloric acid (MCA) using Mucobromic acid (MBA) as an internal standard. The analysis is by GC/MS with EI using a Varian 400 GC/MS which employs a Paul-style ion trap.

I am having trouble with the linearity of response on the instrument while running in GC/MS/MS. I have played around with the charge on the filament, the bonus to the EMV, and the number of ions I try to allow to enter the trap, and although optimizing these can improve my signal, the relationship between concentration and signal is never linear.

I have been preparing a calibration curve (note, I also need to derivatize the compounds by heating them at 70 at concentrations of 50 ppb to 2 ppm of MX. I can run these samples in GC/MS without fragmentation and can get a linear calibration curve over this concentration range.

A previous student was initially able to get relatively linear calibration curves for both compounds in GC/MS (with less than optimized conditions), but this seemed to degrade over time.

Is it possible that something has gotten dirty, and that this would effect GC/MS/MS operation but not GC/MS operation?

Any advice you could provide would be greatly appreciated.

Thanks so much,

Jules Carlson

[gapeev]

Try turning off automatic gain control (ACG). Adjust ion accumulation time to get the usual (target) number of ions around the middle of calibration curve. The rationale is that while going through MS and MS^2 stages the instrument "assumes" that number of ions remains constant over duration of one cycle.

With LC-MS (not UPLC) one rarely faces this discrepancy as typical peak width >10 sec. In GC-MS, ion population can easily change by a factor of two over just a second. Hence actual number of ions will differ from the value predicted by prescan function.

This will of course reduce the dynamic range..
Hope it makes sense.