Tips on getting ES-MS detector response for small molecules?

[Incitor]

I have an LC-MS in ESI mode. The problem I'm having is that I'm not getting a response from the MS detector for most analytes. The mass range for my analytes (the known ones anyway) is 144-154. I'm seeing peaks on the DAD but only noise on the MS. Any thoughts? Do I have to switch to CI?

I have an agilent 1100 HPLC with G1946D single quad in ESI and I'm running reverse phase separation with water/acetonitrile and a C18 column.

[tom jupille]

I'm no mass spectrometrist, but (in very general terms) ESI ionization essentially occurs in solution (inside the solvent droplets), so it's probably a good idea to have *some* buffer in the mobile phase. Also, not all molecules are sufficiently acidic/basic to ionize under ESI conditions, in which case APCI may be required.

[Incitor]

I'm no mass spectrometrist, but (in very general terms) ESI ionization essentially occurs in solution (inside the solvent droplets), so it's probably a good idea to have *some* buffer in the mobile phase. Also, not all molecules are sufficiently acidic/basic to ionize under ESI conditions, in which case APCI may be required.

Thanks for the tip. Yeah, I've thought about that, I will give it a try and see if that works. If not, I'm going to have to switch to APCI.

[lmh]

what are the analytes? Not everything ionises well in ESI. Also remember that if they're very small and volatile, they will dry off just like the solvent does...

[Incitor]

what are the analytes? Not everything ionises well in ESI. Also remember that if they're very small and volatile, they will dry off just like the solvent does...

My analytes are not that volatile. They remain after a rotovap.

Actually, I added 0.1% v/v acetic acid and it really improved the signal from the MS. I'm going to try formic acid next to see if it does any better.