Metabolite identification high performance liquid chromatography

Nobilis, M. et al., Identification and determination of phase II nabumetone metabolites by high-performance liquid chromatography with photodiode array and mass spectro-metric detection, J. Chromatogr. A, 1031(1-2), 229, 2004. 

Mullen W, Hartley RC, Crozier A. Detection and identification of 14C-labeled flavonol metabolites by high-performance liquid chromatography-radiocoxmting and tandem mass spectrometry. J Chromatogr A 2003 1007 21-29. 

Hosoda K, Furuta T, Yokokawa A, Ogura K, Hiratsuka A, Ishii K. Plasma profiling of intact isoflavone metabolites by high-performance liquid chromatography and mass spectrometric identification of flavone glycosides daidzin and genistin in human plasma after administration of kinako. Drug Metab Dispos 2008 36 1485-1495. 

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)... 

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. 

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. 

Nicholson, J. K., Lindon, J. C., Scarfe, G. B., Wilson, I. D., Abou-Shakra, F., Sage, A. B., and Castro-Perez, J. (2001). High-performance liquid chromatography linked to inductively coupled plasma mass spectrometry and orthogonal acceleration time-of-flight mass spectrometry for the simultaneous detection and identification of metabolites of 2-bromo-4-trifluoromethyl. Anal. Chem. 73 1491-1494. 

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. 

Many of the most important chemical questions in the pharmaceutical industry involve the analysis of complex mixtures. Identification of low-level metabolites and drug substance impurities usually requires high-performance liquid chromatography for the separation of these mixtures or isolation of a compound of interest from a sample matrix. In these analyses, the structural information obtainable for the low-level compounds is limited by the type of detection used. The coupling of HPLC and mass spectrometry has become routine and provides useful molecular weight and fragmentation information, but this is often not enough for complete structure elucidation. 

Chromatographic Methods of Analysis High Performance Liquid Chromatography, p. 526. Metabolite Identification in Drug Discovery,... 

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). 

WM Muck, JD Henion. High-performance liquid chromatography/tandem mass spectrometry Its use for the identification of stanozolol and its major metabolites in human and equine urine. Biomed Environ Mass Spectrom 19 37, 1990. 

T Anzai, et al. Separation and identification of methotrexate and its metabolites, 7-hydromethotrexate and polyglutamates, in human tissues by reversed phase high performance liquid chromatography coupled with radioimmunoassay. J Chro-matogr-Bio 415 445, 1987. 

Vree, T.B. van der Ven, AJ.A.M. Verwey-van Wissen, C.P.W.G.M. van Ewijk-Beneken Kolmer, E.W.J. Swolfs, A.E.M. van Galen, P.M. Amatdjais-Groenen, H. Isolation, identification and determination of sulfamethoxazole and its known metabolites in human plasma and urine by high-performance liquid chromatography. J.Chromatogr.B, 1994, 658, 327-340... 

Efficient detection and rapid characterisation of natural products play an important role as an analytical support in the word of phytochemists. The identification of a metabolite at the earliest stage of separation is a strategic element for guiding an efficient and selective isolation procedure. In this respect, the role of hyphenated techniques such as high performance liquid chromatography coupled to mass spectrometry (LC/MS) or to nuclear magnetic resonance (LC/NMR) has became of great interest. 

Benoit, E. Jaussaud, P. Besse, S. Videmann, B. Courtot, D. Delatour, P. Bonnaire, Y. Identification of a benzhydrolic metabolite of ketoprofen in horses by gas chromatography-mass spectrometry and high-performance liquid chromatography. J.Chromatogr., 1992, 583, 167—173 [plasma SPE gradient extracted metabolites LOQ 500 ng/mL LOD 100 ng/mL pharmacokinetics horse]... 

Holcapek M, Kolarova L, Nobilis M. High-performance liquid chromatography-tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites. Anal Bioanal Chem 2008 391 59-78. 

---