Mass spectrometry metabolite profiling

Smedsgaard, J. Frisvad, J. C. Using direct electrospray mass spectrometry in taxonomy and secondary metabolite profiling of crude fungal extracs. I. Microbiol. Meth. 1996,25,5-17. 

Denkert C, Budczies J, Kind T, et al. Mass spectrometry-based metabolic profiling reveals different metabolite patterns in invasive ovarian carcinomas and ovarian borderline tumors. Cancer Res. 2006 66 10795-10804. 

Multiple mass analyzers exist that can perform tandem mass spectrometry. Some use a tandem-in-space configuration, such as the triple quadrupole mass analyzers illustrated (Fig.3.9). Others use a tandem-in-time configuration and include instruments such as ion-traps (ITMS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICRMS or FTMS). A triple quadrupole mass spectrometer can only perform the tandem process once for an isolated precursor ion (e.g., MS/MS), but trapping or tandem-in-time instruments can perform repetitive tandem mass spectrometry (MS ), thus adding n 1 degrees of structural characterization and elucidation. When an ion-trap is combined with HPLC and photodiode array detection, the net result is a profiling tool that is a powerful tool for both metabolite profiling and metabolite identification. 

Zlatkis, A., Bertsch, W., Lichtenstein, H.A., Tishbee, A., Shunbo, F., Liebich, H.M., Coscia, A.M. and Fleischer, N. (1973) Profile of volatile metabolites in urine by gas chromatography-mass spectrometry. Anal. Chem. 45, 763-767. 

While the clinical use of MS/MS of hormonal steroids is new, metabolite analysis by gas chromatography (GC)-mass spectrometry (MS) has been available for 40 years, since few immunoassays were developed for urinary analytes. Profile analysis is a very powerful technique and it must be recognized that with few exceptions, all disorders of steroid synthesis and metabolism first had their metabolome defined... 

The system relies upon preliminary fractionation of the microbial crude extract by dualmode countercurrent chromatography coupled with photodiode array detection (PDA). The ultraviolet-visible (UV-Vis) spectra and liquid chromatography-mass spectrometry (LC-MS) of biologically active peaks are used for identification. Confirmation of compound identity is accomplished by nuclear magnetic resonance (NMR). Use of an integrated system countercurrent chromatography (CCC) separation, PDA detection, and LC-MS rapidly provided profiles and structural information extremely useful for metabolite identification (dereplication, Figure 14.1). 

Hong, Y-J, Mitchell E. 2005. Metabolic profiling of flavonol metabolites in human urine by liquid chromatography and tandem mass spectrometry. J Agric Food Chem 52 6794-6801. 

Mass spectrometry is also being used to help assess the ability of the dmg to reach the target location in the body (McLean et al., 2007 Cornett et al., 2008 Kertesz and Van Berkel, 2008). The ability to determine the presence of the dmg in the target organ, and even the dmg/metabolite profile within the target organ, is explored in Chapter 12. 

Josephs, J. L., Grubb, M. F., Yang, Y., and Humphreys, G. W. (2008). A rapid approach to quantitative in vivo metabolite profiling without the need for authentic standards or labeled compounds. In Proceedings of the 56th ASMS Conference on Mass Spectrometry and Allied Topics, Denver, Co. 

Kieser, B., Impey, G., Meyer, D. F., Caraiman, D., and Gamache, P. (2004). Metabolite profiling utilizing an in-line electrochemical system for LC/MS. Poster presented at 52nd ASMS Conference on Mass Spectrometry and Allied Topics, Nashville, TN. 

Superior sensitivity, efficiency, and specificity have made high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the predominant analytical technique for characterization and quantitative analysis of metabolites (Kostiainen et al., 2003 Ma et al., 2006 Prakash et al., 2007). Ion trap, triple-quadrupole, and quadmpole time-of-flight (Q-TOF) mass spectrometers are routinely used to profile and characterize metabolites in plasma and excreta (Ma et al., 2006). The combination of scan types and features available on mass spectrometers of different design (product ion, MS", neutral loss, precursor ion scans, accurate mass measurements) allows identification and characterization of putative and unexpected metabolites with or without little prior knowledge of biotransformation pathways of a given dmg molecule. 

Lim, H. K., Chan, K. W., Sisenwine, S., and Scatina, J. A. (2001). Simultaneous screen for microsomal stability and metabolite profile by direct injection turbulent-laminar flow LC-LC and automated tandem mass spectrometry. Anal. Chem. 73 2140-2146. 

Jensen et al. [125] investigated an HPLC/ICP-MS (inductively coupled plasma mass spectrometry) with sulfur-specific detection, as a method for obtaining metabolite profiles for omeprazole administered as a 1 1... 

Rochat B et al (2008) Imatinib metabolite profiling in parallel to imatinib quantification in plasma of treated patients using liquid chromatography-mass spectrometry. J Mass Spectrom... 

Van der Greel J, Leegwater DC. 1983. Urine profile analysis by field desorbtion mass spectrometry, a technique for detecting metabolites of xenobiotics. Biomed Mass Spec 10(1 ) 1-4. 

In what many consider to be a landmark publication on metabolomics, Fiehn et al. (2000) state it is crucial to perform unbiased (metabolite) analyses in order to define precisely the biochemical function of plant metabolism. The authors argue that for metabolomics/metabolite profiling to become a robust and sensitive method suited to automation, a mature technology such as gas chromatography-mass spectrometry (GC-MS) is required as an analytical technique. The authors go on to describe a simple sample preparation and analysis regime that allowed for the detection and quantification of more than 300 compounds from a single-leaf sample extract. 

But are there other endogenous substrates for this enzyme A method based on separation techniques and mass spectrometry has been developed to identify endogenous substrates of enzymes by analysis of metabolomes from wild-type and enzyme-inactivated organisms [316], Indeed, the accumulation of metabolites resulting from the inactivation of the enzyme would be considered candidate endogenous substrates for this enzyme. This method based on comparative metabolomics is called discovery metabolites profiling (DMP). 

Cordell, R.L. et al. Quantitative profiling of nucleotides and related phosphate-containing metabolites in cultured mammalian cells by liquid chromatography tandem electrospray mass spectrometry. J. Chromatogr. B. 2008, 871,115-124. 

Fraser, P.D. Enfissi, E.M.A. Goodfellow, M. Eguchi, T. Bramley, P.M. 2007. Metabolite profiling of plant carotenoids using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Plant J. 49 552-564. 

R. Xu, E. Duchoslav, A. Aparicio, E. B. Jones, and D. B. Kassel, Streamlined approaches to metabolic stability assessment and metabolite profiling in drug discovery, in 51st ASMS Conference on Mass Spectrometry and Allied Topics, Montreal, Canada, Book of Abstracts, ASUS, 2003. 

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