The Origin and Implications of Artifact Ions in Bioanalytical LC–MS

Liquid chromatography–mass spectrometry (LC–MS) with electrospray ionization (ESI) is a widely used bioanalytical technique with both qualitative and quantitative applications. Ions are created by electrically charging a stream of droplets from the LC system, which evaporate and leave ions that are transferred to the mass spectrometer. Ideally, these are only from the analyte, but background ions, such as metals, impurities and coeluted species, can react with analytes producing adducts, such as [M + Na]+, [M + K]+, and multimers (2M + H+, 3M + H+, and so forth). Although well known, the extent of adduct ion formation and the implications for quantitative analysis and analyte characterization by tandem MS (MS/MS) are not fully appreciated. We summarize the problem and identify areas that should be considered when developing or using electrospray LC–MS.