State-of-the-art in atmospheric pressure photoionization for LC/MS.

This review presents our perspective on the state-of-the-art of atmospheric pressure photoionization (APPI) for LC/MS. Its focus is on APPI's capabilities and how to utilize them fully. The introduction includes a brief recounting of the history of APPI's development, as well as a summary of its operating principles and current position in the field. The primary ionization mechanisms in APPI are then addressed, including direct analyte photoionization (PI), dopant/solvent PI, and thermospray. Next a summary of the ion-molecule reaction pathways available for analyte ionization is presented, along with the conditions required for activating them. APPI's performance characteristics are then examined. In effect, this review is an interim report on progress made since Rafaelli and Saba concluded that "The ability...to direct the preferential ion formation towards one particular type...can be extremely useful for qualitative and quantitative determinations. For this purpose, a better insight in the processes involved in the ionization step is strongly needed" [A. Raffaelli, A. Saba, Mass Spectrom. Rev. 22 (2003) 318]. In the conclusion, we focus on areas of APPI technology identified as being either unoptimized or largely unexplored, and having the potential to be improved upon-the crux being that with further research and development improvements in the performance, capabilities, and ease-of-use of APPI may reasonably be anticipated.