Utility of multivariate analysis in support of in vitro metabolite identification studies: retrospective analysis using the antidepressant drug nefazodone

References

• Anthony ML, Sweatman BC, Beddell CR, Lindon JC, Nicholson JK. (1994). Pattern recognition classification of the site of nephrotoxicity based on metabolic data derived from proton nuclear magnetic resonance spectra of urine. Mol Pharmacol. 46:199–211.
   PubMed Web of Science ®Google Scholar
• Baillie TA. (2009). Approaches to the assessment of stable and chemically reactive drug metabolites in early clinical trials. Chem Res Toxicol. 22:263–66.
   PubMed Web of Science ®Google Scholar
• Bauman JN, Frederick KS, Sawant A, Walsky RL, Cox LM, Obach RS, Kalgutkar AS. (2008). Comparison of the bioactivation potential of the antidepressant and hepatotoxin nefazodone with aripiprazole, a structural analog and marketed drug. Drug Metab Dispos. 36:1016–29.
   PubMed Web of Science ®Google Scholar
• Bruce SJ, Jonsson P, Antti H, Cloarec O, Trygg J, Marklund SL, Moritz T. (2008). Evaluation of a protocol for metabolic profiling studies on human blood plasma by combined ultra-performance liquid chromatography/mass spectrometry: From extraction to data analysis. Anal Biochem. 372:237–49.
   PubMed Web of Science ®Google Scholar
• Dalvie D, Obach RS, Kang P, Prakash C, Loi CM, Hurst S, Nedderman A, Goulet L, Smith E, Bu HZ, Smith DA. (2009). Assessment of three human in vitro systems in the generation of major human excretory and circulating metabolites. Chem Res Toxicol. 22:357–68.
   PubMed Web of Science ®Google Scholar
• Fabian J, Lehr M. (2007). Normal-phase HPLC and HPLC-MS studies of the metabolism of a cytosolic phospholipase A2a inhibitor with activated ketone group by rat liver microsomes. J Pharm Biomed Anal. 43:601–5.
   Google Scholar
• Idborg H, Edlund P-O, Jacobsson SP. (2004). Multivariate approaches for efficient detection of potential metabolites from liquid chromatography/mass spectrometry data. Rapid Commun Mass Spectrom. 18:944–54.
   PubMed Web of Science ®Google Scholar
• Ivosev G, Burton L, Bonner R. (2008). Dimensionality reduction and visualization in principal component analysis. Anal Chem. 80:4933–44.
   PubMed Web of Science ®Google Scholar
• Janiszewski JS, Rogers KJ, Whalen KM, Cole MJ, Liston TE, Duchoslav E, Fouda HG. (2001). A high-capacity LC/MS system for the bioanalysis of samples generated from plate-based metabolic screening. Anal Chem. 73:1495–501.
   PubMed Web of Science ®Google Scholar
• Jones E, Ma J, Sasaki TA. (2006). Metabolic interspecies comparison by LCMS and principle component analysis. Paper presented at the 54th Conference on Mass Spectrometry and Applied Topics: Poster TP04, Seattle, WA, USA.
   Google Scholar
• Kalgutkar AS, Vaz ADN, Lame ME, Henne KR, Soglia J, Zhao SX, Abramov YA, Lombardo F, Collin C, Hendsch ZS, Hop CECA. (2005). Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P450 3A4. Drug Metab Dispos. 33:243–53.
   PubMed Web of Science ®Google Scholar
• Krug D, Zurek G, Schneider B, Garcia R, Mueller R. (2008). Efficient mining of myxobacterial metabolite profiles enabled by liquid chromatography-electrospray ionization-time-of-flight mass spectrometry and compound-based principal component analysis. Analytica Chimica Acta 624:97–106.
   Google Scholar
• Leclercq L, Cuyckens F, Mannens GS, de Vries R, Timmerman P, Evans DC. (2009). Which human metabolites have we MIST? Retrospective analysis, practical aspects, and perspectives for metabolite identification and quantification in pharmaceutical development. Chem Res Toxicol. 22:280–93.
   PubMed Web of Science ®Google Scholar
• Li AC, Gohdes MA, Shou WZ. (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. 21:1421–30.
   PubMed Web of Science ®Google Scholar
• Lutz U, Lutz RW, Lutz WK. (2006). Metabolic profiling of glucuronides in human urine by LC/MS/MS and partial least-squares discriminant analysis for classification and prediction of gender. Anal Chem. 78:4564–71.
   Google Scholar
• Mayol RF, Cole CA, Luke GM, Colson KL, Kerns EH. (1994). Characterization of the metabolites of the antidepressant drug nefazodone in human urine and plasma. Drug Metab Dispos. 22:304–11.
   PubMedGoogle Scholar
• Nicholson JK, Lindon JC, Holmes E. (1999). ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29:1181–9.
   PubMed Web of Science ®Google Scholar
• Peterman SM, Duczak NJr, Kalgutkar AS, Lame ME, Soglia JR. (2006). Application of a linear ion trap/orbitrap mass spectrometer in metabolite characterization studies: examination of the human liver microsomal metabolism of the non-tricyclic anti-depressant nefazodone using data-dependent accurate mass measurements. J Am Soc Mass Spectrom. 17:363–75.
   PubMed Web of Science ®Google Scholar
• Plumb RS, Stumpf CL, Granger JH, Castro-Perez J, Haselden JN, Dear GJ. (2003). Use of liquid chromatography/time-of-flight mass spectrometry and multivariate statistical analysis shows promise for the detection of drug metabolites in biological fluids. Rapid Commun Mass Spectrom. 17:2632–8.
   PubMed Web of Science ®Google Scholar
• Qian K, Yu D, Chen C-H, Huang L, Morris-Natschke SL, Nitz TJ, Salzwedel K, Reddick M, Allaway GP, Lee K-H. (2009). Anti-AIDS agents. 78. Design, synthesis, metabolic stability assessment, and antiviral evaluation of novel betulinic acid derivatives as potent anti-human immunodeficiency virus (HIV) agents. J Med Chem. 52:3248–58.
   PubMed Web of Science ®Google Scholar
• Rotzinger S, Baker GB. (2002). Human CYP3A4 and the metabolism of nefazodone and hydroxynefazodone by human liver microsomes and heterologously expressed enzymes. Eur Neuropsychopharmacol. 12:91–100.
   Google Scholar
• Sangster TP, Wingate JE, Burton L, Teichert F, Wilson ID. (2007). Investigation of analytical variation in metabonomic analysis using liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom. 21:2965–70.
   Google Scholar
• Tolonen A, Turpeinen M, Pelkonen O. (2009). Liquid chromatography-mass spectrometry in in vitro drug metabolite screening. Drug Discov Today 14:120–33.
   PubMed Web of Science ®Google Scholar
• Von Moltke LL, Greenblatt DJ, Granda BW, Grassi JM, Schmider J, Harmatz JS, Shader RI. (1999). Nefazodone, meta-chlorophenylpiperazine, and their metabolites in vitro: cytochromes mediating transformation, and P450-3A4 inhibitory actions. Psychopharmacology (Berlin) 145:113–22.
   PubMed Web of Science ®Google Scholar
• Wang C, Kong H, Guan Y, Yang J, Gu J, Yang S, Xu G. (2005). Plasma phospholipid metabolic profiling and biomarkers of type 2 diabetes mellitus based on high-performance liquid chromatography/electrospray mass spectrometry and multivariate statistical analysis. Anal Chem. 77:4108–16.
   PubMed Web of Science ®Google Scholar
• Werner E, Croixmarie V, Umbdenstock T, Ezan E, Chaminade P, Tabet JC, Junot C. (2008). Mass spectrometry-based metabolomics: accelerating the characterization of discriminating signals by combining statistical correlations and ultrahigh resolution. Anal Chem. 80:4918–32.
   PubMed Web of Science ®Google Scholar
• Zhou N, Zeller W, Zhang J, Onua E, Kiselyov AS, Ramirez J, Palsdottir G, Halldorsdottir G, Andresson T, Gurney ME, Singh J. (2009). 3-Acrylamide-4-aryloxyindoles: synthesis, biological evaluation and metabolic stability of potent and selective EP3 receptor antagonists. Bioorg Med Chem Lett. 19:1528–31.
   Google Scholar
• Zhu M, Ma L, Zhang D, Ray K, Zhao W, Humphreys WG, Skiles G, Sanders M, Zhang H. (2006). Detection and characterization of metabolites in biological matrices using mass defect filtering of liquid chromatography/high resolution mass spectrometry data. Drug Metab Dispos. 34:1722–33.
   PubMed Web of Science ®Google Scholar