Any way to slow down MS/MS fragmentation?

[tayzyboy]

Hi, (fairly new to MS/MS so please be patient with me)

We have a Waters Quattro premier and have been running several compounds with daughter scans.
However two compounds we have have been difficult to determine a suitable MRM.
Using the daughter scan with infusion (in methanol) we get no fragmetation at low collision energies, and as soon as the energy is taken over a certain level (roughly 20) the compound fragments into about 10+ other compounds. Overall this means that our MRM is less sensitive than an SIR.
We are primarily interested in sensitivity (<500pg/ml) as our LC method is very selective for the compounds.

Is there anything i can do to produce only one or two fragments to increase MRM sensitivity?

[Peter Apps]

If you only want one fragment then monitor the parent ion - exploit the selectivityof the LC rather than relying on the MS-MS.

Peter

[Kostas Petritis]

Tayzyboy,

There are compounds like the ones that you are analyzing and there is no much you can do about it. From the moment that you investigated different collision energies (with a step of 1 or 2) and you are not able to get any major fragment there are no other MS settings that you can play to increase your MRM sensitivity.

You could try to make a complex/adduct and then fragment it to recover your molecular ion but it would be fairly complicated and there might issues with the quantitation...

[james little]

If you mean absolute counts, then splitting into 10 signals in MS/MS is not good. But in MS/MS, often the Signal/noise ratio can increase even though the absolute signal decreases. Depends on the chemical noise from the instrument from solvents, column bleed, etc..

You didn't say whether using M+H or some other adduct. Addition of ammonium acetate might give you the ammonium adduct which could give you different fragmentation?

Also, you might take a look at the compound in negative ion mode.