Towards a universal detector for small molecule application: Direct-EI in LC-MS.

This article describes the operating principles of the direct-electron ionization (EI) interface, which is becoming more popular in many LC-MS applications. Matrix effects and the role of direct-EI as a universal detector for small molecule analysis are also discussed in detail. The advantages and drawbacks of this approach are described and a comparison with atmospheric pressure ionization (API) interfaces is made. The potential of direct-EI is illustrated with a selection of practical applications

Profiling of non-esterified fatty acids in human plasma using liquid chromatography-electron ionization mass spectrometry

This paper focuses on the development of a novel approach to analyze underivatized fatty acids in human plasma. The method is based on liquid–liquid extraction followed by reversed phase liquid chromatography coupled to direct-electron ionization mass spectrometry (LC-Direct-EI-MS). The assay is validated. Calibrations show satisfactory linearity and precision in the investigated range of linearity. Recoveries span from 75% to 104%. The method limits of detection, varying from 0.53 to 5.35 μM, are satisfactory for the quantitation of non-esterified fatty acids (NEFAs) in plasma at physiological levels. The method has been successfully applied to the NEFAs profiling of plasma samples from healthy adult volunteers and subjects affected by diabetes mellitus. Compared with published protocols based on gas chromatography–mass spectrometry and liquid chromatography coupled to electrospray ionization mass spectrometry, this method does not require derivatization and does not show matrix effects, thus simplifying sample preparation procedure and reducing the total time of analysis to approximately 90 min. In addition, Direct-EI-MS allows the acquisition of highquality NIST library-matchable EI spectra, allowing an easy-to-obtain identification of the target NEFAs

AN OVERVIEW OF MATRIX EFFECTS IN LIQUID CHROMATOGRAPHY–MASS SPECTROMETRY

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