What are some of the main differences between APCI and ESI MS ionization modes, and how will this affect LC/MS method development?

There are a few major differences between APCI and ESI modes of ionization that are especially important in LC-MS method development:

With APCI-MS compounds are ionized in the gaseous state, so generally only compounds with relatively small molecular weights (<1 kD) can be analyzed.

Also, mobile phase buffers have less of a suppressive effect on ionization than in ESI where compounds are ionized in the liquid state.

Therefore, APCI is generally a better means of ionization in IEC separation methods where buffers are required for analyte elution.

ESI, however, does allow for the analysis of much larger compounds, such as proteins. Another significant difference is that low polarity compounds, analyzed with normal phase solvent systems, can be detected with APCI but are not sufficiently ionized by ESI.