Matrix small-molecule MALDI

McCombie, G., and Knochenmuss, R. (2004). Small-molecule MALDI using the matrix suppression effect to reduce or eliminate matrix background interferences. Anal. Chem. 76 4990-4997. 

Matrix Choices for Small-Molecule MALDI 369 Table 9.1 Summary of approaches for small-molecules analysis using MALDI-MS. 

More recently, Brennan has shown that FAC-MALDI-MS can be used to screen small molecules, relying upon MRM transitions to overcome the chemical noise generated by the matrix [16]. This is an acceptable approach for known compounds, but for ligand discovery from uncharacterized mixtures, ion selection... 

This desorption ionisation technique leads to weak fragmentation. The analyte is incorporated into a solid organic matrix (such as hydroxybenzoic acid) and the mixture is placed on a sample holder that is irradiated with UV laser pulses (e.g. N2 laser, A = 337 nm, pulse width = 5 ns). The laser energy is absorbed by the matrix and transferred to the analyte, which becomes desorbed and ionised (Fig. 16.18c). Although MALDI is considered to be a soft ionisation technique, a substantial amount of energy is involved. Because the technique involves pulsed ionisation, it is well suited for time-of-flight mass analysis of biomolecules. The analysis of small molecules (M < 500 Da) is limited because the matrix decomposes upon absorption of the laser radiation. However, solid supports such as silicone can be used as the matrix to overcome this disadvantage. 

Yang, M., James, A., Covey, T., and Kovarik, P. (2005). High-speed automated deposition of matrix onto tissue samples for small molecule imaging application using MALDI MS/MS. In Proceedings of the 53 rd ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX. 

Carbon nanotubes are another new material being exploited as novel matrices for MALDI, particularly in the analysis of small molecules offering excellent sensitivity and reproducibility, as few matrix background ions are observed.45 47... 

Use of Matrix Assisted Laser Desorption/ Ionization Imaging Mass Spectrometry (MALDI-IMS) in the Development of Novel Small Molecule Drugs... 

Matrix selection The successful detection of analyte molecules depends on the correct choice of the MALDI matrix. The matrix must not react with the analyte in the tissue sections. The MALDI matrices generally used for MALDI-TOF-MS are CF1CA, SA, and DF1B. For small molecule drugs, CHCA and DF1B are the most widely used matrices [125],... 

MALDI is achieved in two steps. In the first step, the compound to be analysed is dissolved in a solvent containing in solution small organic molecules, called the matrix. These molecules must have a strong absorption at the laser wavelength. This mixture is dried before analysis and any liquid solvent used in the preparation of the solution is removed. The result is a solid solution deposit of analyte-doped matrix crystals. The analyte molecules are embedded throughout the matrix so that they are completely isolated from one another. 

Metabolites are small molecules that participate as substrates or products in metabolic reactions essential for the normal function of a cell. This molecular class comprises a wide range of compounds, from amino acids to lipids, organic acids, and nucleotides (11). The wide range of concentration and different chemical properties make the analysis of these compounds a challenging task. Usually, high-resolution mass spectrometers and chemical derivatization strategies are necessary to resolve isobaric interferences, increase ionization efficiency, and overcome chemical background effects from the matrix-assisted laser desorption/ionization (MALDI) matrix or the tissue matrix itself (12). 

In addition to MALDI, matrix-free LDI techniques have been proved to be useful in IMS studies of small molecules (62). Thus, NIMS has also been proved to be a highly sensitive matrix-free method (in which functionalized surfaces are used to absorb the laser, eliminating the need for matrices) for tissue imaging in metabolomics (75,76). It has been described that NIMS surface can be easily treated or modified with different chemical initiators. As a result, distinct metabolite profiles from the same biological sample can be obtained. For instance, coating NIMS surface with cationization agents... 

One drawback for the use of MALDI with small molecules is that sample preparation is more intensive than that for electrospray because of the need for matrix addition. To some extent this sample preparation can, however, be automated. A more significant drawback is the presence of a low-mass-noise background arising from the matrix. This noise background can interfere with the direct assessment of the spectrum for the compound of interest. Considerable research efforts have been directed at approaches that eliminate the low-mass... 

More success was obtained using on-line solid phase extraction before offline analysis by capillary electrophoresis with matrix-assisted laser-desorption ionization (MALDI) MS [18]. Because microdialysis is a method used for analysis of small molecules and peptides, MALDI is not used frequently with microdia lysis sampling. Another disadvantage is that MALDI cannot be used on-line with the separation because it is a vacuum ionization technique. However, if the pep-tide is large enough (0 1000 Da) MALDI can be useful. For the analysis of peptides in dialysate an appropriate separation is important before mass spectrometric detection. In a comparison with direct sampling of dialysate in MALDI, capillary electrophoresis provides the high efficiency separations necessary to resolve all... 

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