Tandem mass spectrometry metabolite identification

Castiglioni S, Zuccato E, Crisci E, Chiabrando C, Fanelly R, Bagnati R (2006) Identification and measurement of illicit drugs and their metabolites in urban wastewater by liquid chromatography-tandem mass spectrometry. Anal Chem 78 8421-8429... 

Figure 5.40 Product-ion spectrum of the (M + H)+ ion (m/z 614) of Indinavir with the proposed origins of the ions observed. Reprinted by permission of Elsevier Science from Identification of in vitro metabolites of Indinavir by Intelligent Automated LC-MS/MS (INTAMS) utilizing triple-quadrupole tandem mass spectrometry , by Yu, X., Cui, D. and Davis, M. R., Journal of the American Society for Mass Spectrometry, Vol. 10, pp. 175-183, Copyright 1999 by the American Society for Mass Spectrometry.

Li L et al. (2006) Liquid chromatography-tandem mass spectrometry for the identification of L-tetrahydropalmatine metabolites in Penicillium janthinellum and rats. Biomed Chromatogr 20(1) 95-100... 

Urpi-Sarda M, Jauregui O, Lamuela-Raventos RM, Jaeger W, Miksits M, Covas MI and Andres-Lacueva C. 2005. Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry. Anal Chem 77(10) 3149—3155. 

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. 

As a consequence, for unequivocal identification of the constituents of complex mixtures found in surfactant blends and also in the analyses of surfactants and their metabolites in environmental samples, MS and tandem mass spectrometry (MS-MS) have proved to be more advantageous and are discussed thoroughly in Chapter 2. To optimise the output of reliable results and to save manpower and time certain procedures in sample preconcentration, clean-up and separation prior to MS examinations are inevitable. These are discussed in the present book in more detail in Chapter 3. 

Dear G. Plumb R. Mallet D. Use of monolithic silica columns to increase analytical throughput for metabolite identification by liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry, 2001, 15, 152-158. 

Prokai L, Zharikova AD. 1998. Identification of synaptic metabolites of dynorphin A (1-8) by electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 12 1796. 

Hop, C. E., Tiller, P. R., and Romanyshyn, L. (2002). In vitro metabolite identification using fast gradient high performance liquid chromatography combined with tandem mass spectrometry. Rapid Commun. Mass Spectrom. 16 212-219. 

Tiller, P. R., Yu, S., Castro-Perez, J., Fillgrove, K. L., and Baillie, T. A. (2008). High-throughput, accurate mass liquid chromatography/tandem mass spectrometry on a quadrupole time-of-flight system as a first-line approach for metabolite identification studies. Rapid Commun. Mass Spectrom. 22 1053-1061. 

Blum, W., Aichholz, R., Ramstein, P., Kuhnol, J., Bruggen, J., O Reilly, T., andFlorsheimer, A. (2001). In vivo metabolism of epothilone B in tumor-bearing nude mice Identification of three new epothilone B metabolites by capillary high-pressure liquid chromatography/ mass spectrometry/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 15 41-49. 

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. 

Lee, M. S. Yost, R. A. 1988. Rapid identification of drug metabolites with tandem mass spectrometry. Biomed. Env. Mass Spectrom., 15,193-204. 

Lopez, L. L. Yu, X. Cui, D. Davis, M. R. 1998. Identification of drug metabolites in biological matrices by intelligent automated liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom., 12,1756-1760. 

Gjerde J, Kisanga ER, Hauglid M, Holm PI, Mellgren G, Lien EA (2005) Identification and quantification of tamoxifen and four metabolites in serum by liquid chromatography-tandem mass spectrometry. J Chromatogr A 1082 6-14... 

Adducts with macromolecules, particularly proteins, offer long-lived biological markers of exposure to Chemical Warfare Agent (CWA), possibly up to several months. Gas or liquid chromatography combined with tandem mass spectrometry, are the methods of choice for unequivocal identification of these adducts or metabolites at trace levels. Several... 

X Yu, D Cui, MR Davis. Identification of in vitro metabolites of Indinavir by intelligent automated LC-MS/MS (INTAMS) utilizing triple quadrupole tandem mass spectrometry. J Am Soc Mass Spectrom 10 175—183, 1999. 

Dear, G. Plumb, R. Mallett, D. Use of Monolithic Silica Columns to Increase Analytical Throughput for Metabolite Identification by Liquid Chromatography/Tandem Mass Spectrometry, Rapid Comm. Mass Spectrom. 15, 152-158 (2001). 

Lee, M.S. Yost, R.A. Rapid Identification of Drug Metabolites with Tandem Mass Spectrometry, . Biomed. Environ. Mass Spectrom. 15, 193-204 (1988). 

Yu, X. Cui, D. Davis, M.R. Identification of In Vitro Metabolites of Indinavir by Intelligent Automated LC-MS/MS (INTAMS) Utilizing Triple Quadrupole Tandem Mass Spectrometry, J. Am. Soc. Mass Spectrom. 10, 175-183 (1999). 

Hop, C.E. Tiller, PR. Romanyshyn, L. In Vitro Metabolite Identification Using Fast Gradient High Performance Liquid Chromatography Combined with Tandem Mass Spectrometry, Rapid Commun. Mass Spectrom. 16(3), 212-219 (2002). 

---