(1) Negative ion formation and signal response can be improved by choosing the right solution chemistry. One method to improve solvent desolvation and reduce the electrical discharge (noise) is to add isopropyl alcohol (2-Propanol) to the mobile phase. Reported in the literature nearly twenty years ago, as little as a 10% solution has been found to increase the signal level and decrease the noise level under many conditions. The addition of methanol to the mobile phase also can improve the signal, though usually not to the same degree as IPA.
(2) Another technique used to improve ionization involves the pH of the solution or mobile phase used. Higher pH values are often better. Post column addition of a basic solution which adds proton acceptors to the mix, such as ammonium hydroxide (20 or 30 mM), can also improve signal response and stability.
(3) APCI mode: If running nonpolar to semi-polar small molecular weight compounds, especially those which are volatile, this is still the source of choice. *Conventional ESI mode is best for polar to neutral molecules in small to large Mw ranges.