We have been having a disagreement about the sensitivity of an ESI interface for LC-MS as a function of MP composition. Conventional wisdom states that a higher organic modifier concentration in the MP enhances ionization efficiency and sensitivity. I believe that this is true for the flow rates encountered with "standard" LC columns (i.e. >2.1 mm ID, flow rates >200 uL/min). I have heard, however, that the opposite is true with flow rates encountered with small bore and capillary columns (<50 uL/min); that higher aqueous concentration enhance ionization effieciency. Does anyone know if this is true, and if so, if you could point me to some references to show my colleagues? Thanks.

This is not as simple a question as it sounds on the surface. In ESI ions need to be made in solution. Water easily supports the formation of these ions, but its solvation energy makes ion desorption more difficult. As the organic content is increased, it becomes harder to make make (and keep) ions in solution, but desorption is much easier. In cases of very high organic content (with some solvents and not others) it is almost impossible to make ions. As for the comments on flow rate, lower flow rates generally enhance ionization and the effects of MP composition will still follow the same rules (just an opinion based on observations, no data to back it up).

Hi Roy,
I aggre with the last statement of the anonymous. For flow rates I have worked as low as 2-3 microL/min it seems that a high percentage of organic modifier stabilises the spray and increase ion extraction and sensitivity.

Now, that could also depend from other additives that you may have in the mobile phase. For exemple I have noticed that in the case of amino acids for high acetonitrile concentrations (75:25 ACN:H2O) I had a suppression of ion signal if my mobile phase did not contain an acid (formic) [J. Chromatogr. A 913 (2001) 331-340]. But now the majority of people that uses LC-MS puts some additives in the mobile phase, and of course that could be a particular compound dependent case.

Now if you are the type of person "I'll show you my point of view" and you have the adequate instrumentation that is easy to prove for your compounds of interest. Just take the compounds of interest, 2 mobile phase water and acetonrile in which the compounds will be dissolved (and an additive if you want), no column, just something to create a backpressure and make a gradient from water to acetonitrile with both systems by following with the MS signal of your compounds.

This will give you the general tendance, but I still believe that if you had a chromatographic peak you would further gain from the better signal to noise ratio with high acetonitrile concentrations.

Hope the above helps.

Kostas