Liquid Chromatography 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... 

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. 

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. 

The prediction of retention times in a given eluent from log P has been proposed for aromatic hydrocarbons.19 The log A values of phenols21 and nitrogen-containing compounds22 were also related to their logP, and the calculated log P was used for the qualitative analysis of urinary aromatic acids, i.e. for the identification of metabolites in urine from the differences of log P in reversed-phase liquid chromatography.23,24... 

S. Suwanrumpha, R. B. Freas, Identification of Metabolites of Ampicillin Using Liquid Chromatography/Thermospray Mass Spectrometry and Fast Atom Bombardment Tandem Mass Spectroscopy , Biomed. Environ. Mass Spectrom. 1989, 18, 983-994. 

Kratzsch C, Peters FT, Kraemer T, Weber AA, Maurer HH. 2003. Screening, library-assisted identification and validated quantification of fifteen neuroleptics and three of their metabolites in plasma by liquid chromatography/ mass spectrometry with atmospheric pressure chemical ionization. J Mass Spectrom 38 283. 

Pelander, A. Ojanpera, 1. Laks, S. Rasanen, 1. Vuori, E. Toxicological Screening with Formula-Based Metabolite Identification by Liquid Chromatography/Time-of-Flight Mass Spectrometry. Anal. Chem. 2003, 75, 5710-5718. 

Nassar AEF, Bjorge SM, Lee DY. On-line liquid chromatography-accurate radioisotope counting coupled with a radioactivity detector and mass spectrometer for metabolite identification in drug discovery and development. AnaZyft caZ Chemistry 75, 785-790, 2003. 

Fig. 6.2.2a-bc High-performance liquid chromatography (HPLC) with electrochemical (EC) detection of neurotransmitter metabolites, a standard mixture b cerebrospinal fluid (CSF) sample - control c CSF sample - aromatic amino acid decarboxylase (AADC) deficiency. Peak identification 1 = 5HIAA (7.7 min), 2 = 3-MD (9.6 min), 3 = HVA (11.7 min)... 

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). 

E Zomer, J Quintana, J Scheemaker, S Saul, SE Charm. High-performance liquid chromatography-receptorgram—a comprehensive method for identification of veterinary drugs and their active metabolites. ACS Symp Ser 636 149-160, 1996. 

Gu, M., Wang, Y., Zhao, X. G., and Gu, Z. M. (2006). Accurate mass filtering of ion chromatograms for metabolite identification using a unit mass resolution liquid chromatography/ mass spectrometry system. Rapid Commun. Mass Spectrom. 20 764-770. 

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. 

Kantharaj, E., Ehmer, P. B., Tuytelaars, A., Van Vlaslaer, A., Mackie, C., and Gilissen, R. A. (2005b). Simultaneous measurement of metabolic stability and metabolite identification of 7-methoxymethylthiazolo[3,2-a]pyrimidin-5-one derivatives in human liver microsomes using liquid chromatography/ion-trap mass spectrometry. Rapid Commun. Mass Spectrom. 19 1069-1074. 

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. 

Li, A. C., Gohdes, M. A., and Shou, W. Z. (2007). N-in-one strategy for metabolite identification using a liquid chromatography/hybrid triple quadrupole linear ion trap instrument using multiple dependent product ion scans triggered with full mass scan. Rapid Commun. Mass Spectrom. 21 1421-1430. 

Liu, D. Q., Xia, Y. Q., and Bakhtiar, R. (2002). Use of a liquid chromatography/ion trap mass spectrometry/triple quadrupole mass spectrometry system for metabolite identification. Rapid Commun. Mass Spectrom. 16 1330-1336. 

Wrona, M., Timo, M., Bateman, K. P., Mortishire-Smith, R. J., and O Connor, D. (2005). All-in-one analysis for metabolite identification using liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry with collision energy switching. Rapid... 

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. 

Corcoran, O., Nicholson, J. K., Lenz, E. M., Abou-Shakra, F., Castro-Perez, J., Sage, A. B., and Wilson, I. D. (2000). Directly coupled liquid chromatography with inductively coupled plasma mass spectrometry and orthogonal acceleration time-of-flight mass spectrometry for the identification of drug metabolites in urine Application to diclofenac using chlorine and sulfur detection. Rapid Commun. Mass Spectrom. 14 2377-2384. 

Yoshitsugu, H., Fukuhara, T., Ishibashi, M., Nanbo, T., and Kagi, N. (1999). Key fragments for identification of positional isomer pair in glucuronides from the hydroxylated metabolites of RT-3003 (Vintoperol) by liquid chromatography/electrospray ionization mass spectrometry. J. Mass Spectrom. 34 1063-1068. 

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. 

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