Best Practice in Mass Spectrometry for LC‐MS

Gas chromatography—mass spectrometry (GC-MS) became a routine analytical technique by the late 1960s. Today, liquid chromatography-mass spectrometry (LC-MS) enables routine qualitative and quantitative analyses of a variety of pharmaceuticals and biomedical compounds that is limited by solubility instead of volatility. Electrospray and atmospheric pressure chemical ionization (APCI) have become the most widely used ionization sources and interfaces for high performance liquid chromatography (HPLC) during drug discovery and development and post-approval therapeutic drug monitoring (TDM) using MS. Unlike early LC-MS interfaces and ionization sources such as thermospray, particle beam, and continuous-flow fast atom bombardment, electrospray and APCI interfaces operate at atmospheric pressure. To facilitate the analysis of compounds that do not ionize efficiently using electrospray or APCI, a UV ionization technique called atmospheric pressure photoionization (APPI) has been developed for use with LC-MS and ultrahigh pressure liquid chromatography-mass spectrometry (UHPLC-MS).