For analysis of compounds that ionize poorly by ESI and APCI, the atmospheric pressure photoionization (APPI) source provides a useful alternative. It combines Agilent’s proven orthogonal spray nebulization and counterflow drying gas with innovative photoionization from Syagen Technology. The long-lasting krypton lamp emits photons at energy levels high enough to ionize many large classes of compounds, but low enough to minimize the ionization of air and common HPLC solvents. Relatively low ionization energy means the APPI source causes minimal fragmentation and generates mostly molecular ions and protonated molecules.