A Method for the Analysis of Low-Mass Molecules by MALDI-TOF Mass Spectrometry

Abstract

We report a novel method termed matrix suppressed laser desorption/ionization to improve the analysis of low-mass molecules by MALDI-TOF mass spectrometry. In this method, the surfactant of cetrimonium bromide (CTAB) is added to the conventional matrix of r-cyano-4-hydroxycinnamic acid solution to prepare the MALDI samples. During the MALDI process, the presence of CTAB could substantially or even completely suppress the matrixrelated ion background. As a result, very clean mass spectra can be routinely obtained in the low-mass range. In addition, the presence of CTAB can significantly improve the mass resolution of low-mass molecules. It is seen that high-quality spectra were routinely obtained at a matrix/CTAB ratio of 1000:1. This method has been successfully used to analyze a variety of low-mass molecules.Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has become a very powerful tool to analyze large synthetic polymers and biomolecules. 1 However, it has been a challenge to use MALDI for the analysis of low-mass analytes (m/z <500 Da). This challenge is due in part to the presence of a variety of abundant matrix-related ions in the low-mass range of spectra, because most of the currently used matrixes have molecular weights less than 300, and during laser irradiation, they also act as their own matrixes, producing a variety of matrix-related ions. This can also limit the utility of MALDI-TOF in several important applications, including the automated, high-throughput combinatorial and chip-array analysis.Considerable efforts have been made and several alternative approaches have been developed to overcome this problem. The first is a matrix-free approach in which the sample substrate acts as matrix. 2-5 For example, Buriak et al. 2 reported successful laser desorption/ionization on porous silicon (DIOS). Surface-enhanced neat desorption (SEND) introduced by Hutchens and Yip 5 is another matrix-free method for small molecule analysis.The second approach utilizes high-mass matrix molecules. 6,7 Ayorinde et al. 6 studied the use of high-mass porphyrin derivatives to replace conventional low-mass molecules such as R-cyano-4-hydroxycinnamic acid (CHCA) as the MALDI matrixes. They successfully demonstrated the use of mesotetrakis(pentafluorophenyl)porphyrin (F20TPP, MW 974.57) as a matrix for the MALDI-TOF analysis of low-mass surfactants. With F20TPP as the matrix, the fatty acids of saponified vegetable oils were also successfully analyzed. 7 The third approach uses inorganic compounds instead of organic molecules as matrix. 8-16 In 1988, Tanaka et al. 8 first reported the use of ultrafine metal powder in protein analysis. Since then, many inorganic materials, including graphite particles, 9-12 fine metal or metal oxide powder, 13 silver thin-film substrates or particles, 14 and silica gel, 15 have been used in the MALDI-TOF analysis of low-mass molecules. Schurengberg et al. 16 systematically investigated the particle suspensions, which include different particle materials, particl...

Efficient Analysis of Non-Polar Environmental Contaminants by MALDI-TOF MS with Graphene as Matrix

“…However, it is difficult to analyze small molecules with conventional matrix due to matrix ion interference. Recently, porous silicon [12][13][14][15], matrix with high molecular weight [16,17], surfactant-suppressed matrix [18], and inorganic materials [19][20][21] have been successfully employed in the analysis of small molecules. However, there are no reports about the analysis of nonpolar PAHs by MALDI-TOF due to their great difficulty in ionization, though metal-assisted LDI analysis of nonpolar polyethylene was reported [22].…”

Gold nanoparticles as assisted matrices for the detection of biomolecules in a high-salt solution through laser desorption/ionization mass spectrometry

“…Although many groups have demonstrated that the use of an organic chemical matrix in MALDI-TOF-MS is capable of detecting peptides, proteins, and nucleic acids [2], there are still unresolved problems in the general application of MALDI-TOF-MS: (1) The cocrystallization of analytes with matrices does not produce homogeneous mixtures, which cause hot spots and thereby require sweet-spot searching [3]. (2) MALDI-TOF-MS is incapable of detecting small molecules because of the high background signals of small organic matrices, which are present in the low-mass region (Ͻ500 Da) [4]. (3) The presence of salts in a sample solution will increase the intensities of salt-adducted forms [5].…”

An Overview of Analytical Applications of Time of Flight-Mass Spectrometric (TOF-MS) Analyzers and an Inductively Coupled Plasma-TOF-MS Technique

“…[27][28][29][30][31][32][33][34][35] Recent works dealing with the use of the technique to the identification and structural analysis of various compounds can be mentioned. [36][37][38][39][40][41][42][43][44][45][46][47][48] Coupling of MALDI with liquid chromatography, capillary electrophoresis (CE) and gel chromatography is a way to extend its applicability. 32,[49][50][51][52][53][54][55][56][57][58] The possibility to attain the sensitivity of physical limits (a few atoms or molecules) by laser-assisted reflectron TOF-MS has been stated.…”