Non-volatile salts LC-MS

[Xcalibur]

hi all,

i have a "problem" regarding an LC-MS/MS method for pegylated acrylate monomers. I started method dev with water/methanol/formic acid on a ESI-QQQ. All analytes that are not charged by itself are ionized as [M+Na]+ only, no [M+H]+ or other adducts. adding ammonium formate did not improve the situation, as i got a 7/3- mixture of sodium and ammonium adduct and traces of [M+H]+. I want to get rid of the Na-adducts as i observed that there is only very little fragmentation and SRM-transitions are weak, thus LoD is bad.
I started to add Li-formate (10 µM) which works like a charm, however, a non-volatile salt in ESI-MS

As I extended the calibration range of the method (was 0.5-100 ng/mL) to 500 ng/mL I realized that calibration curves start to flatten out at the top end and I think this is due to Li-ion shortage (10 µM = 500 ng/mL for a MW 500 compound) and there are 50+ analytes present (MW 150 to 1500).

What do you think is a concentration of non-volatile salt which is still "safe" to handle? Can I go to 100 µM?
Does anyone have experience with LC-MS and non-volatile buffers/salts?

Thanks
Georg

[bunnahabhain]

I have once used 100 µg/L sodium formate and had no problems. Try to use a divert valve to keep the flow away from the ion source as much as possible.

[Rndirk]

All analytes that are not charged by itself are ionized as [M+Na]+ only, no [M+H]+ or other adducts. adding ammonium formate did not improve the situation, as i got a 7/3- mixture of sodium and ammonium adduct and traces of [M+H]+. I want to get rid of the Na-adducts as i observed that there is only very little fragmentation and SRM-transitions are weak,

This sounds like a perfect situation for embracing the sodium adducts! You will have a hard to getting rid of them anyway if they're so eager to ionize as sodium adducts.

Did you optimize (increase) the collision energy to induce fragmentation? You could also try to increase the collision pressure.

To answer the original question, I believe you could safely increase the concentration of Li-formate to 0.1-1mM. But I suggest to work with the sodium adducts.

Did you check ESI (-) performance for your compounds?

Try to use a divert valve to keep the flow away from the ion source as much as possible.

A very good point! Only load the MS if it *needs* to measure.

[Xcalibur]

This sounds like a perfect situation for embracing the sodium adducts! You will have a hard to getting rid of them anyway if they're so eager to ionize as sodium adducts.

Seems tempting, I know, but all SRM optimization (also neg) was not as sensitive as the Li-adducts and I need a low LoD for certain species.

Divert valve is a good point!

Thanks
Georg

[Rndirk]

You sparkled my interest: Generally speaking, do sodium adducts produce less fragments compared to proton adducts of the same molecule? And if so, why?

I've googled around a bit and if someone is interested check the links:

https://www.researchgate.net/post/Why_i ... S_analysis

viewtopic.php?t=19273

In these discussions there is no real consensus. Some people believe the sodium adducts are more stable during fragmentation events, while others claim the opposite. The explanation that dissociation of sodium adducts produce more neutral fragments (because the charge stays with sodium) sounds to me like the more logical one. If this is the case, sodium adducts show the same or even more fragmentation, but you just don't detect them because they aren't charged.

I don't know how different the situation is for different classes of molecules: can this discussion even be generalized?

If someone has more input on this matter with possibly a literature source?