Mass Spectrometry Detection in Comprehensive Liquid Chromatography: Basic Concepts, Instrumental Aspects, Applications and Trends

The review, as can be deduced from the title, focuses on both theoretical and practical aspects of the use of mass spectrometry as a third, added dimension to a comprehensive LC (LCxLC) system, generating the most powerful analytical tool today for non-volatile analytes. The first part deals with the technical requirements for linkage of an LCxLC system to an MS one, including the choice of the mobile phase (buffer and salts), flow rate (splitting), type of ionization (interface); advantages and disadvantages of off-line and on-line methods are discussed, as well. A discussion of the various aspects of instrumentation is provided, both from a chromatographic and mass spectrometry standpoint, with particular emphasis directed to the choice of column sets, spatial resolution, mass resolving power, mass accuracy, and tandem-MS capabilities. The extent to which mass spectrometry may be of aid in unraveling column-outlet multicompound bands is highlighted, along with its effectiveness as a chromatographic detector of excellent sensitivity, universality yet with potential in terms of selectivity and amenability to quantitative analysis over a wide dynamic range. The following section of the review contains significant applications of comprehensive two-dimensional LC coupled to MS in different areas of research, with details on interfaces, column stationary phases, modulation and MS parameters. It is not the intention of the authors to provide a comprehensive description of the techniques, but merely to discuss only those aspects which are essential for successful applications of the LC–MS combination. The reader will be acquainted with the enormous potential of this hyphenated technique, and the factors and instrumental developments that have concurred to make it emerge to a central role in specialized fields, such as proteomics.