Infusion mass spectrometry

McDougall G, Martinussen I and Stewart D. 2008. Towards fruitful metabolomics high throughput analyses of polyphenol composition in berries using direct infusion mass spectrometry. J Chromatogr B 871(2) 362-369. 

Direct infusion mass spectrometry is a popular technique used by medicinal chemists to check the molecular mass of target compounds. In... 

Peris-Vicente J, Garrido-Medina R, Sim6-Alfonso E, Gimeno-Adelantado JV, Domenech-Carbo MT (2007) Infusion mass spectrometry as a fingerprint to characterize varnishes in oil pictorial artworks. Rapid Commun Mass Spectrom 21 851-856. 

Different analytical chemistry methods are used for analysis of the metabolome (Figure 3). Direct-infusion mass spectrometry (DI-MS) on both, low and (ultra)high resolution MS, infuses raw metabolite extracts in the mass spectrometer without prior chromatography or electrophoretic separation and often uses high-resolution mass spectrometers. This method offers fast analysis with low duty cycles however, isomeric and isobaric substances cannot be... 

Boemsen, K.O., Gatzek, S., andlmbert, G., Controlled protein precipitation in combination with chip-based nanospray infusion mass spectrometry. An approach for metabolomics profiling of plasma, Anal. Chem., 77(22), 7255, 2005. 

Evidence for the presence of covalent adducts involving proanthocyanidins and anthocyanidins was also observed by infusion mass spectrometry. These minor ions appeared in two series, one series starting at m/z 781 and one at m/z 783. Each of these series is observable up to m/z 2509/2511, with ions separated by a mass of 288 (Figure 4). Based upon previous studies and speculation, these ions were consistent with two types of anthocyanin-proanthocyanidin adducts. Specifically, these ions agree with the direct condensation products of... 

Castrillo, J. L. Hayes, A. Mohammed, S. Gaskell, S. J. Oliver, S. G. An optimized protocol for metabolome analysis in yeast using direct infusion electrospray mass spectrometry. Phytochemistry 2003, 62, 929-937. 

K.L. Vikse, M.P. Woods, J.S. Mclndoe, Pressurized sample infusion for the continuous analysis of air- and moisture-sensitive reactions using electrospray ionization mass spectrometry, Organometallics 29 (2010) 6615-6618. 

However, phosphate salts are not volatile. We must constantly remember that mass spectrometry is a gas-phase experiment. Materials to be examined by mass spectrometry must ultimately be made gaseous. Figure 19.14 shows the atmospheric pressure ionization source chamber of a mass spectrometer after infusion of a 20 mM potassium phosphate-containing mobile phase into the instrument for a few hours. The accumulation of phosphate salts on the striker plate is evident. Visual evidence of salt accumulation is also apparent on the back wall of the source chamber, above the striker plate. The overall haziness of the image is not the result of poor photography, but rather due to the coating of dust on the inner walls of the chamber and all surfaces within. 

Lewis DA, Guzzetta AW, Hancock WS, Costello M. 1994. Characterization of humanized anti-TAC, an antibody directed against the interleukin 2 receptor, using electrospray ionization mass spectrometry by direct infusion, LC/MS, and MS/MS. Anal Chem 66 585. 

Very low flow electrospray is called nanoelectrospray [26] where the samples are infused into the mass spectrometer at the nanoliter flow rate range. The infusion of a few microliters will result in a stable signal for more then 30 min, using pulled capillaries or chip-based emitters [27]. With infusion, signal averaging allows to improve the limit of detection in tandem mass spectrometry. Nanoelectrospray is particularly important in combination with nanoflow liquid chromatography or chip-based infusion for the analysis of peptides and proteins. 

Hopfgartner, G. The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites. Rapid Commun. Mass Spectrom. 2005, 19, 618-626. 

Mass spectrometry enables the type of direct analyses described, but it does have its limitations. Online operation forces detection at infusion concentrations, in salty buffer and under complex mixture conditions. General ion suppression results from the buffer and mixture components, and mixture complexity can tax the resolution of even the best mass spectrometers. Increasing compound concentration is not the answer, as this leads to problems of solubility and increased compound consumption. We have found that the online method can work successfully for up to 100 compounds per analysis, but the false negative rate becomes appreciable [21]. As an alternative for ligand discovery purposes, we have developed a FAC-LC/MS system in which FAC effluent is sampled and analyzed by LC/MS [19]. This system offers the ability to concentrate mixture components and introduces another dimension to the data in order to tolerate more complex mixtures (Fig. 6.9). Using this system, we have screened approximately 1000 modified trisaccharide acceptor analogs targeting immobilized N-... 

Figure 14.5 Modified-ESI source for the direct infusion of undiluted ILs. A stainless steel wire is placed in the spray, leading to the optimal vaporization of the IL. Additionally, an orthogonal ESI source is used. Only a part of the IL ions is transferred into the MS, thus minimizing pollution of the source. (Modified from Dyson, R J. et al.. Direct probe electrospray (and nanospray) ionization mass spectrometry of neat ionic liquids. Chem. Commun., 2204, 2004. Reproduced by permission of the Royal Society of Chemistry.)...

The most recent modification of the NBD-Cl method involves a further improvement in its qualitative support (616). It involves the infusion of the extract employed for thin-layer chromatography via an electrospray interface into a mass spectrometer operating in the multiple-stage mass spectrometry mode, thus allowing confirmation of suspect results. The cleanup of the thyroid gland samples was also performed with a selective extraction procedure, based on the specific complex formation of the thiouracil, methylthiouracil, propylthiouracil and phenylthiouracil, tapazole, and mercaptobenzimidazole residues with mercury ions bound in a Dowex 1-X2 affinity column. 

Erve, J. C. L., DeMaio, W., and Talaat, R. E. (2008). Rapid metabolite identification with sub parts-per million mass accuracy from biological matrices by direct infusion nanoelectrospray ionization after clean-up on a ZipTip and LTQ/Orbitrap mass spectrometry. Rapid... 

Ackermann, B. L., and Dethy, J. M. (2005). Understanding the role and potential of infusion nanoelectrospray ionization for pharmaceutical hioanalysis. In Using Mass Spectrometry for Drug Metabolism Studies (Korfmacher, W. A., Ed.). CRC Press, Boca Raton, pp. 329-356. 

Dethy, J. M., Ackermann, B. L., Delatour, C., Henion, J. D., and Schultz, G. A. (2003a). Demonstration of direct bioanalysis of drugs in plasma using nanoelectrospray infusion from a silicon chip coupled with tandem mass spectrometry. Anal. Chem. 75 805-811. 

Kapron, J. T., Pace, E., Van Pelt, C. K., and Henion, J. (2003). Quantitation of midazolam in human plasma by automated chip-based infusion nanoelectrospray tandem mass spectrometry. Rapid Common. Mass Spectrom. 17 2019-2026. 

In lipidomics, MS can be used either by direct infusion, that is, by the so-called shotgun MS, or in combination with chromatographic separation, typically LC and sometimes also with GC. Both approaches have their own advantages and limitations. Most targeted lipid analyses are performed with liquid chromatography coupled to mass spectrometry (LC-MS), while the use of gas chromatography-mass spectrometry (GC-MS) is utilized only for the analysis of fatty acids and some steroids. In addition, surface analysis by MS has been applied in lipid analysis of intact tissues. 

In the authors and several other OPCW-designa-ted laboratories, LC/MS is used as the initial screening procedure for water samples and aqueous extracts of matrices such as soil. This usually provides a tentative identihcation of polar analytes within half a day, on the basis of molecular mass, any fragment ions present, and retention time. A second analysis, under LC/MS/MS conditions, usually provides a firmer identihcation on the basis of a limited number of product ions, most of which result from simple neutral losses. With clean matrices, the initial screening may be performed even faster using how injection or infusion rather than LC (14). An example of the application of how injection with electrospray ionization/mass spectrometry (ESI/MS) in an OPCW prohciency test is provided by Hooijschuur et al. (21) The identihcation of the analytes is usually conhrmed by GC/MS (in most cases after derivatization) as the second technique. 

K. E. 0degard, W. Lund, Multi-element speciation of tea infusion using cation-exchange separation and size-exclusion chromatography in combination with inductively coupled plasma mass spectrometry, J. Anal. Atom Spectrom., 12 (1997), 403-408. 

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