Mass spectrometry and nuclear magnetic resonance

Mass spectrometry (MS) and nuclear magnetic resonance (NMR) are most widely used technologies for CDs identification. Fast atom bombardment mass spectrometry (FAB-MS),matric-assisted laser desorption ionization time-of-flight mass spectrometry (MALDITOF MS) are used for CDs molecular weight detection, from which to identify the DP range of CD. NMR is used for CDs structure identification. 

Nakagawa, T, K Ueno, M Kashiwa and J Watanabe (1994). The stereoselective synthesis of cyclomaltopentaose. A novel cyclodextrin homologue with D.P. five. Tetrahedron Letters, 35,921-1924. 

K Fukase and S Kusumoto (2002). Chemical synthesis of cyclodextrins by using intramolecular glycosylation. Journal of Organic Chemistry, 67,8182-8190. 

YD Lee and HS Kim (1993). Enzymatic production of cyclodextrins from milled corn starch in an ultrafiltration membrane bioreactor. Biotechnology and Bioengineering, 41, 88-94. 

Nakano, H and S Kitahata (2005). Application of cyclodextrin glucanotransferase to the synthesis of useful oligosaccharides and glycosides. In Handbook of Industrial Biocatalysis, T Hou Ching (ed.), pp. 22-1-22-17. CRC Press. 

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The development and reports of methods for colorless chlorophyll derivative (RCCs, FCCs, and NCCs) analysis are relatively recent and the structures of the compounds are being elucidated by deduction from their chromatographic behaviors, spectral characteristics (UV-Vis absorbance spectra), mass spectrometry, and nuclear magnetic resonance analysis. The main obstacle is that these compounds do not accumulate in appreciable quantities in situ and, moreover, there are no standards for them. The determination of the enzymatic activities of red chlorophyll catabolite reductase (RCCR) and pheophorbide a monoxygenase (PAO) also helps to monitor the appearance of colorless derivatives since they are the key enzymes responsible for the loss of green color. ... 

Sweeley, C.C., and Nunez, H.A. (1985) Structural analysis of glycoconjugates by mass spectrometry and nuclear magnetic resonance spectroscopy. Annu. Rev. Biochem. 54, 765-801. 

Bob Ardrey obtained a first degree in Chemistry from the University of Surrey where he went on to obtain his doctorate studying the chemistry of trans-2,3-dichloro-l,4-dioxan and the stereochemistry of its reaction products using primarily mass spectrometry and nuclear magnetic resonance spectroscopy. He then carried out post-doctoral research at King s College, London, into the development of emitters for field-desorption mass spectrometry. 

J.-L. Wolfender, S. Rodriguez and K. Hostettmann, Liquid chromatography coupled to mass spectrometry and nuclear magnetic resonance spectroscopy for the screening of plant constituents. J. Chromatogr.A 794 (1998) 299-316. 

A structure-based approach for discovering protein ligands and for drug design by coupling size exclusion chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. Anal. Chem. 2001, 73, 571-581. 

The determination of polyphenolics may result in interference due to co-elution of phenolic acids and procyanidins. This problem can be eliminated by fractionation of polyphenolics into acidic and neutral polyphenolics prior to sample injection into the HPLC system. Because the fractionation techniques effectively improve the resolution of many polyphenolic peaks in the reversed-phase HPLC system, it is suggested that further characterization and identification of unknown peaks be conducted by additional methods such as mass spectrometry and nuclear magnetic resonance. 

Preparative HPLC is another convenient method for isolating degradants from excipient compatibility matrices (72,73). The peaks from stressed samples can be collected, the solvent removed with a rotary evaporator, and the remaining solution lyophilized to obtain purified compounds. The samples can then be analyzed by other methods such as mass spectrometry and nuclear magnetic resonance (NMR) in order to identify the molecular composition. 

Mopper, K., Stubbins, A., Ritchie, J. D., Bialk, H. M., and Hatcher, P G. (2007). Advanced instrumental approaches for characterization of marine dissolved organic matter Extraction techniques, mass spectrometry, and nuclear magnetic resonance spectroscopy. Chem. Rev. 107,419-442. 

Kosir IJ, Lapornik B, Andrensek S, Wondra AG, Vrhovsek U and Kidric J, Identification of anthocyanins in wines by liquid chromatography, liquid chromatography-mass spectrometry and nuclear magnetic resonance. Anal Chim Acta 513 277-282 (2004). 

C. E. Brown, S. C. Roerig, V. T. Berger, R. B. Cody, and J. M. Fujimoto, "Analgesic Potencies of Morphine 3- and 6-Sulfates After Intracerebroventricular Adminstration in Mice Relationship to Structural Characteristics Defined by Mass Spectrometry and Nuclear Magnetic Resonance," J. Pharm. Sci., 24, 821 (1985). 

Stronger chemical evidence for the presence of a dithiolene in molybdopterin was obtained when the mild alkylation reagent iodoacetamide effectively trapped the dithiolene (65). This reaction yielded a derivative whose characterization by FAB mass spectrometry and nuclear magnetic resonance (NMR) was consistent with the structure shown in Fig. 5. The method appeared to leave the side chain intact and preserved the pterin oxidation state. From this experiment the view persisted that molybdopterin is a disubstituted dithiolene bearing a reduced pterin and a short chain terminated with a phosphate. 

As stated above, any number of analytical tools lend themselves to the acquisition of metabolomics data. A brief description of two major tools, mass spectrometry and nuclear magnetic resonance, follow. 

As the glucose is metabolized, the metabolic derivatives become enriched with the isotopic carbon label and are detected using advanced technologies such as mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. Importantly, incorporation of isotopes into molecules can alter reaction mechanisms including the rate of a reaction-this is termed isotopic substitution and forms the basis of the kinetic isotope effect. 

Ramm, M. et al. Rapid analysis of nucleotide-activated sugars by high-performance liquid chromatography coupled with diode-array detection, electrospray ionization mass spectrometry and nuclear magnetic resonance. J. Chromatogr. A. 2004, 1034,139-148. 

G. J. Lehr, T. L. Barry, G. Petzinger, G. M. Hanna, S. W. Zito, Isolation and identification of process impurities in trimethoprim drug substance by high-performance liquid chromatography, atmospheric pressure chemical ionization liquid chro-matography/mass spectrometry and nuclear magnetic resonance spectroscopy, J. Pharm. Biomed. Anal. 19 (1999), 373-389. 

Endogenous ligands for the cannabinoid receptor have not yet been identified. Arachidonylethanolamide, a new arachidonic acid derivative named anandamide, was isolated from porcine brain. Its structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. It inhibits the specific binding of a labelled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands, and produces a concentration-dependent inhibition of the electrically-evoked twitch response of the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. Similar compounds were synthesized and their pharmacological properties were investigated. 

This multidisciplinary team approach toward impurity identification was successfully applied to the identification of this impurity. Each and every discipline played a very important role. Without SPE enrichment to remove the drug substance from the impurities, the impurity could not be purified by preparative HPLC. The novel acidic degradation study of the impurity provided very valuable information of the structure of the impurity. Mass spectrometry and nuclear magnetic resonance spectroscopy were the ultimate tools in this structure elucidation. Furthermore, the formation mechanisms were concluded by a careful examination of the process. 

Gerhold et al. (9) developed research techniques to Identify the biochemical metabolite which conditioned resistance. They used the same plant materials that had been Included In Winner s genetic studies and Stark s research. All plants were grown from seed and were maintained without the use of pesticides. Included In their study was a resistant parent, a homozygous recessive susceptible parent, and their hybrid. In addition, they tested a susceptible parent which had one dominant locus for resistance. Basically their technique Involved the collection of exudate and subsequent analysis by gas- and high-performance-liquid chromatography, mass spectrometry, and nuclear magnetic resonance (NMR) spectroscopy. 

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