Matrix-dependent signal suppression or enhancement represents a major drawback in quantitative analysis with liquid chromatography coupled to atmospheric pressure ionization mass spectrometry (LC-API-MS). Because matrix effects (ME) might exert a detrimental impact on important method parameters (limit of detection, limit of quantification, linearity, accuracy, and precision), they have to be tested and evaluated during validation procedure. This review gives a detailed description on when these phenomena might be expected, and how they can be evaluated. The major sources of ME are discussed and illustrated with examples from bioanalytical, pharmaceutical, environmental, and food analysis. Because there is no universal solution for ME, the main strategies to overcome these phenomena are described in detail. Special emphasis is devoted to the sample-preparation procedures as well as to the recent improvements on chromatographic and mass spectrometric conditions. An overview of the main calibration techniques to compensate for ME is also presented. All these solutions can be used alone or in combination to retrieve the performance of the LC-MS for a particular matrix-analyte combination.

A major limitation in quantitative analysis with electrospray ionization mass spectrometry (ESI-MS) is represented by the so-called matrix effects in which the matrix coextracted with the analytes can alter the signal response, causing either suppression or enhancement, resulting in poor analytical accuracy, linearity, and reproducibility. In the direct electron ionization liquid chromatography-mass spectrometry (direct-EI LC-MS) interface the ionization process is based on electron impact ionization, and it occurs in the gas phase and is not influenced by coeluted matrix compounds. In this work we quantitatively evaluated matrix effects on enriched environmental and biological samples, with different extraction procedures, using ESI and direct-EI LC-MS. As expected, the samples analyzed with direct-EI were not affected by matrix composition, whereas with ESI we observed either signal suppression or enhancement, depending on the sample nature.

Water-soluble organic compounds (WSOC) often represent a large fraction of the total organic mass found in the atmospheric aerosol. They play a very important role in determining the ability of aerosol particles to act as cloud condensation nuclei (CCN), influencing cloud and fog formation and cloud albedo. Molecular characterization of WSOC in fogwater samples was achieved using a twostage ion-trap mass spectrometer equipped with electrospray ionization (ESIMS/MS). Negative ionization conditions in the electrospray interface finalized our characterization of the acidic fraction of WSOC that comprises both monoand di-carboxylic acids and polycarboxylic acids for which a similarity was suggested with naturally occurring humic (or fulvic) acids, and which are sometimes referred to in the literature as humic-like substances (HULIS). Molecular structure elucidation was accomplished using several model compounds and exploiting mass spectral resolution for compound separation. Single compound identification was attempted by recording typical MS/MS fragmentation pathways of model substances and comparing them with actual sample pathways in order to establish specific correspondences. Besides this spectrum-matching identification process, MS/MS interpretation led to several hypothetical structures for HULIS, extending the comprehension of their chemical nature. Suwannee River fulvic acid, proposed as a suitable model for representing the complex mixtures of HULIS in cloud and water aerosol extracts, was also analyzed, and the data obtained were compared with those from WSOC.

Major progress in interfacing liquid chromatography and electron ionization mass spectrometry is presented. The minimalism of the first prototype, called the Direct-EI interface, has been widely refined, improved, and applied to modern instrumentation. The simple interfacing principle is based on the straight connection between a nanoHPLC system and a mass spectrometer equipped with an EI source forming a solid and reliable unicum resembling the immediacy and straightforwardness of GC/MS. The interface shows a superior performance in the analysis of small-medium molecular weight compounds, especially when compared to its predecessors, and a unique trait that excels particularly in the following aspects: (1) It delivers high-quality, fully library matchable mass spectra of most sub-1 kDa molecules amenable by HPLC. (2) It is a chemical ionization free interface (unless operated intentionally) with accurate reproduction of the expected isotope ion abundances. (3) Response is never influenced by matrix components in the sample or in the mobile phase (nonvolatile salts are also well accepted). A deep evaluation of these aspects is presented and discussed in detail. Other characteristics of the interface performance such as limits of detections, range of linear response, and intra- and interday signal stability were also considered. The usefulness of the interface has been tested in a few real-world applications where matrix components played a detrimental role with other LC/MS techniques.