Ionization efficiency ladders as tools for choosing ionization mode and solvent in liquid chromatography/mass spectrometry

Rationale The choice of mobile phase components and optimal ion source, mainly electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI), is a crucial part in liquid chromatography/mass spectrometry (LC/MS) method development to achieve higher sensitivity and lower detection limits. In this study we demonstrate how to rigorously solve these questions by using ionization efficiency scales. Methods Four ionization efficiency scales are used: recorded with both APCI and ESI sources and using both methanol‐ and acetonitrile‐containing mobile phases. Each scale contains altogether more than 50 compounds. In addition, measurements with a chromatographic column were also performed. Results We observed a correlation between calibration graph slopes under LC conditions and log IE values in ESI (but not APCI) thereby validating the use of log IE values for choosing the ion source. Most of the studied compounds preferred ESI as an ion source and methanol as mobile organic phase. APCI remains the ion source of choice for polycyclic aromatic hydrocarbons. For APCI, both acetonitrile and methanol provide similar ionization efficiencies with few exceptions. Conclusions Overall the results of this work give a concise guideline for practitioners in choosing an ion source for LC/MS analysis on the basis of the chemical nature of the analytes.