Matrix clusters, MALDI

While MSI can provide images that allow the user to discriminate between drug and metabolite, it is far more difficult to differentiate between isobaric compounds. Due to the complex nature of tissue, many different lipids, peptides, and other biological compounds (not to mention MALDI matrix clusters) can complicate the MSI analysis for drug compounds. Several... 

Endogenous interferences and MALDI matrix cluster can complicate the analysis of xenobiotic drug compounds and their metabolites in MSI. The use of hyphenated techniques (either MS" or IMS) or high-resolution mass spectrometry can serve to increase analyte specificity. Although instrument... 

MALDI is the dominant ionization source choice for MSI however, it is not without drawbacks. The application of MALDI matrix on top of the tissue surface complicates the analysis by adding potentially isobaric matrix cluster ions that may obscure the drug compound. Careful selection of MALDI matrix can reduce the matrix effect. An alternative would be to either use the water native to the tissue as a matrix such as with IR-MALDI or altogether eliminate the need for matrix. DESI is an atmospheric pressure technique that permits the direct analysis of surface samples, including tissue sections, with minimal sample preparation (Takats et al., 2004 Cooks et al., 2006). In contrast to MALDI—MSI, no matrix is required however, the spatial resolution for DESI—MSI is worse when compared to MALDI or SIMS imaging experiments. 

Although many different compounds have been suggested as MALDI matrices, the analysis of lipids with their low molecular weights requires certain special properties of the matrix. For example, it is important that the yields of matrix (or matrix cluster) ions generated by laser irradiation are as low as possible. This is the reason why compounds that undergo photoreactions (especially matrices derived from cinnamic acid such as sinapinic add) should not be used, in order to avoid saturation of the detector by matrix-derived ions. 

Figure 3.11 summarizes such key experimental points. As a first point, we have to choose the appropriate ionization method for the detection of small metabolites, we have alternative choices other than MALDI, such as secondary ion mass spectrometry (SIMS) [15], nanostructure-initiator mass spectrometry (NIMS) [20,21], desorption/ionization on silicon (DIOS) [22], nanoparticle-assisted laser desorptiopn/ ionization (nano-PALDI) [23], and even laser desorption/ionization (LDI) [24,25]. We consider that MALDI is stiU the most versatile method, particularly due to the soft ionization capability of intact analyte. However, other methods each have unique advantages for example, SIMS and nano-PALDI have achieved higher spatial resolution than conventional MALDI-IMS, and above aU, these mentioned alternative methods are all matrix-free methods, and thus can exclude the interruption of the matrix cluster ion. Next, if MALDI is chosen, experimenters should choose a suitable matrix compound, solvent composition, and further matrix application method for their target analyte. All these factors are critical to obtain sufficient sensitivity because they affect efficiency of analyte extraction, condition of cocrystallization, and, above all, analyte-ionization efficiency. In addition, based on the charge state of the analyte molecule, suitable MS polarity (i.e., positive/ negative ion detection mode) should be used in MS measurement. Below, we shall describe the key experimental points for MALDI-IMS applications of representative metabolites. 

MALDI is another soft ionization technique used in MS. MALDI involves a two-step process. First, the firing of an ultraviolet (UV) laser beam induces desorption. In this process, matrix material absorbs the UV laser energy in firing, leading to the ablation of the upper layer ( 1 pm) of the matrix material. The hot plume produced during ablation contains many species neutral or ionized matrix molecules, protonated or deprotonated matrix molecules, and matrix clusters (even nanodroplets). In the... 

MALDI, these low-mass ions often appear in the same mass range as the matrix clusters, confusing their analysis. ... 

Laser-desorption mass spectrometry (LDMS) or matrix-assisted laser desorption ionization (MALDI) coupled to a time-of-flight analyzer produces protonated or deprotonated molecular ion clusters for peptides and proteins up to masses of several thousand. 

Matrix assisted laser desorption ionisation (MALDI) and ESI-MS spectra of non-ionic surfactant blends of AE obtained after positive ionisation were compared [28]. Both the ionisation procedures, which produce [M + Na]+ ion clusters, were very useful for this purpose, but the ESI spectra generated were more complex, whereas MALDI ionisation led to simpler spectra that can be interpreted more easily [28]. 

MALDI matrix spectra are characterized by strong molecular and/or quasi-molecular ion signals accompanied by series of matrix (Ma) cluster ions and some more abundant fragment ions. [32] In positive-ion MALDI, [Man-hH]" cluster ions predominate, while [Ma -H] cluster ions are preferably formed in negative-ion MALDI. The principal ion series may be accompanied by [Ma H-alkali] ions and some fragments of minor intensity, e.g., [Ma H-H-H20]. In particular with aprotic matrices, radical ions may predominate. In addition, a continuous background is... 

Direct evidence of the existence of organomagnesium compounds with a cluster metal core has been obtained by matrix-assisted laser desorption/ ionizaiton time-of-flight mass spectrometry (MALDI-TOF MS). This method allows one to record the spectra of molecular ions [MH]+ of pro-tonated molecules M. The major advantage of this method is that the use of volatile matrices makes it possible to measure the mass spectra of compounds that hardly transform to the gas phase under other conditions. This is true in full measure for organomagnesium compounds. The method does not provide detailed information on the geometry of corresponding... 

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry MALDI-TOF appears the newest technique particularly suitable for the study of oligomers and dendrimers because, under appropriate conditions, the parent peak is obtained uncontaminated by fragmentation species. However, in some cases supramolecular clusters have been observed which could be misinterpre-tated as dimers and higher multiplets [13]. The molecular weight range available reaches 50,000 D with a potential resolution between 0.01 and 0.05%. 

Most analytical studies using FT-ICR mass spectrometry, where ions have been produced inside (or just outside) the analyzer cell, have used lasers as ionization sources. Other than some very limited Cs secondary ion mass spectrometry (SIMS) studies [77], most research utilized direct laser desorption to form various organic [78] and inorganic [79] ions, including metal [80] and semiconductor [81] (including carbon) clusters. More recently matrix assisted laser desorption ionization (MALDI) has been used to form ions of high molecular weight from polymers [82] and many classes of biomolecules [83]. 

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