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Dealing with compound that does not fragment

Posted: Tue Feb 04, 2025 8:07 pm
by alltieear
Hi,

I am working with a mixture of analytes but there is one in particular that is giving me issues. (Agilent 6460 QQQ)

I am able to detect the precursor ion using ms2 scan mode. However, when I try to use Agilent optimizer software, the best fragmentor and CE settings only provides an abundance of ~1900. With product ion scan, the expected product ion is only detected at minimal quantities.

So this leads me to think that the analyte is just resistant to fragmentation and confirmed by spectra information on Pubchem. Reported spectra show the product ion as virtually non existent.

So my questions is how do I deal with this? Do I just live with the low peak integration using the product ion? Or can I use the precursor m/z as the product m/z?

Re: Dealing with compound that does not fragment

Posted: Thu Feb 06, 2025 2:09 pm
by Gaetan Glauser
Hi,

Have you switched to the other ionization mode and confirmed it not better?

Do you have the possibility to use another fragmentation mode than CID?

If the answers are yes and no, then consider the following options (in random order):

1. You do with the very low abundance of the product ion, if this is acceptable for your standards.

2. You perform a SIM analysis on your triple quad (again if it is acceptable based on your standards).

3. You switch to a high resolution MS (if you acces to one) and work in full scan mode.

4. You test if derivatization would be possible

Hope it helps!

Re: Dealing with compound that does not fragment

Posted: Thu Feb 06, 2025 2:13 pm
by JMB
To induce more fragmentation, you need to put more energy into the molecular ion.

You do not give us any details, so here is a selection of options that may, or may not, be viable for you!

1) Increase source temp.

2) Switch from CI to EI

3) Switch from +ve ion mode to -ve ion mode.

4) Increase gas pressure in collision cell

Good Luck!