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.

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Contamination of water resources by organochlorine pesticides (OCPs) continues to receive widespread attention because of the increasing concern regarding their high persistence and bioaccumulation. These organic pollutants are not amenable by liquid chromatography (LC) coupled to atmospheric pressure ionization-mass spectrometry, which represents the method of choice for the characterization of pesticide residues in water. Gas chromatography-mass spectrometry provides excellent response for OCPs, but it falls short when complex, multiresidue analyses are required. As recently demonstrated, an efficient EI-based LC-MS interface can generate very good spectra for an extremely wide range of small-medium molecular weight molecules of different polarity and can represent a valid tool in solving the analytical challenge of analyzing OCPs by LC-MS. Based on this assumption, we present a new approach for the determination of 12 OCPs in water samples. The method requires a solid-phase extraction preconcentration step followed by nanoscale liquid chromatography coupled to a direct-electron ionization direct interface (Direct-EI). Direct-EI is a miniaturized interface for efficiently coupling a liquid chromatograph with an EI mass spectrometer. The capability to acquire high-quality EI spectra in a wide range of concentrations, and to operate in selected ion monitoring mode during analyses, allowed a precise quantification of the OCPs. Without sample injection enrichment, limits of detection of the method span from 0.044 to 0.33 microg/L, corresponding to an instrumental detection limit of 120-850 pg. In addition, a careful evaluation of the matrix effect showed that the response of the Direct-EI interface was never affected by sample interferences. From our knowledge, the proposed method represents the first application of LC-MS in the analysis of organochlorine pesticides.

A miniaturized, aerosol based interface for directly coupling a liquid chromatograph with a mass spectrometer is presented. The interface is entirely within the electron ionization (EI) source of the mass spectrometer and no additional, external devices are needed. This simple and effective approach exploits micro-flow nebulization technology providing a new interface suitable for a variety of applications of environmental and biological interest. The new interface provides necessary linearity, ruggedness, sensitivity, and reproducibility of response for trace level analysis, and readily interpretable mass spectra for unambiguous identification of unknown compounds of small to medium molecular weight. They are the extremes of two different technical approaches: The first one typically employs very high pressure for the efficient separation of analytes dissolved in a sometimes complex liquid phase; the second one, a sophisticated detector for chromatography, measures the mass-to-charge ratio of the analytes and operates at a very high vacuum, a rarefied gas phase with no tolerance for extraneous substances. The characteristics of HPLC and EIMS are often seen as incompatible: The effort of achieving and maintaining the high vacuum required for mass spectrometry operation is in contrast with the intrinsic nature of HPLC, predominantly operating at high solvent flow rates. In addition, the low tolerance of mass spectrometers for non-volatile mobile phase components contrasts with a HPLC dependence on non-volatile buffers to achieve high-resolution separations. The two techniques, which in principle appear totally incompatible, may nevertheless show an impressive number of overlapping applications. Small to medium sized molecules, typically under 1000 u, that for several reasons are suitable for HPLC analysis, can generate highly informative, reproducible, library matchable EI mass spectra for an easier identification and characterization. Thousands of these compounds can be found in many different areas of environmental, biological, or pharmaceutical interest. Therefore, a single analytical tool that combines the two techniques without limiting their potential is highly desirable. Today, most of the commercially available HPLC/MS interfaces are based on the atmospheric pressure ionization technique (API), namely electrospray (ESI) and atmospheric pressure chemical ionization (APCI) [1,2,3,4] in which the ionization of the sample is obtained at atmospheric pressure in the liquid phase and only the ionic species are then admitted into the high vacuum analyzer region. This particular ionization process is considered soft in terms of internal energy, with no fragmentation normally observed. Polarity is a key factor for a satisfying response of ESI and APCI interfaces. Electron ionization, because of the higher internal energy involved, produces several neutral and ionic fragments in a peculiar combination of abundance and mass-to-charge ratio characteristic of each compound as a real chemical fingerprint. EI itself is n...

A novel liquid chromatography-mass spectrometry (LC-MS) interfacing concept is presented and discussed. The new interface, called liquid-EI (LEI), is based on electron ionization (EI) but, differently from any previous attempt, the vaporization of solutes and mobile phase takes place at atmospheric pressure into a specifically designed region, called "vaporization microchannel", before entering the high-vacuum ion source. The interface is completely independent from the rest of the instrumentation and can be adapted to any gas chromatography/mass spectrometry (GC/MS) system, as an add-on for a rapid LC-MS conversion. Pressure drop and temperature gradient between LC and MS were considered to enhance the analyte response and reduce band broadening and/or solute carryovers. A fused silica liner, placed inside the vaporization microchannel, acts as an inert vaporization surface speeding up the gas-phase conversion of large molecules while lessening possible memory effects. The liner is easily replaceable for a quick and extremely simple interface maintenance. Proof of concept and detailed description of the interface are here presented.