The Practice of NMR Spectroscopy in Drug Metabolism Studies

Handbook of Drug Metabolism, Second Edition

Volumn , Issue , 2008, Pages 373-392

  Wilson, Ian D ^a   Lindon, John C ^b   Nicholson, Jeremy K ^b  

^a ASTRAZENECA   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85137909798     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.3109/9781420076486-18     Document Type: Chapter

References (60)

1. Wilson ID, Nicholson JK, Lindon JC. The role of nuclear magnetic resonance spectroscopy in drug metabolism. In: Woolf TF, ed. Handbook of Drug Metabolism. New York: Marcel Dekker, 1999:523-550.
2. Malet-Martino M, Bernadou J, Martino R, Armand JP. 19F NMR spectrometry evidence for bile acid conjugates of alpha-fluoro-beta-alanine as the main biliary metabolites of antineoplastic fluoropyrimidines in humans. Drug Metab Dispos 1988; 16:78-84.
3. Malet-Martino M, Gilard V, Desmoulin F, Martino R. Fluorine nuclear magnetic resonance spectroscopy of human biofluids in the field of metabolic studies of anticancer and antifungal fluoropyrimidine drugs. Clin Chim Acta 2006; 366:61-73.
4. Foxall PJD, Lenz EM, Lindon JC, Neild GH, Wilson ID, Nicholson JK. NMR and HPLC-NMR studies on the toxicity and metabolism of ifosfamide. Ther Drug Monit 1996; 18:498-505.
5. Gabano E, Marengo E, Bobba M, Robotti E, Cassino C, Botta M, Osella D. Pt-195 NMR spectroscopy: a chemometric approach. Coord Chem Rev 2006; 250:2158-2174.
6. Keun HC, Beckonert O, Griffin JL, Richter C, Moskau D, Lindon JC, Nicholson JK. Cryogenic probe C-13 NMR spectroscopy of urine for metabonomic studies. Anal Chem 2002; 74:4588-4593.
7. Losonczi J, Green I. Cryogenically cooled NMR probes: more information in less time. Am Lab 2004; 36:26.
8. Haner RL, Llanos W, Mueller L. Small volume flow probe for automated direct-injection NMR analysis: design and performance. J Magn Reson 2000; 143:69-78.
9. Price KE, Vandaveer SS, Lunte CE, Larive CK. Tissue targeted metabonomics: metabolic profiling by microdialysis sampling and microcoil NMR. J Pharm Biomed Anal 2005; 38:904-909.
10. Keeler J. Understanding NMR Spectroscopy. Chichester, U.K.: J. Wiley and Sons Ltd, 2005.
11. Bales JR, Sadler PJ, Nicholosn JK, Timbrell JA. Urinary excretion of acetaminophen and its metabolites as studied by proton NMR spectroscopy. Clin Chem 1984; 30:1631-1636.
12. Bales JR, Nicholson JK, Sadler PJ. Two dimensional proton nuclear magnetic resonance “maps” of acetaminophen metabolites in human urine. Clin Chem 1985; 31:757-762.
13. Foxall PJD, Parkinson JA, Sadler IH, Lindon JC, Nicholson JK. Analysis of biological fluids using 600 MHz proton NMR spectroscopy: application of homonuclear two-dimensional J-resolved spectroscopy to urine and blood plasma for spectral simplification and assignment. J Pharm Biomed Anal 1993; 11:21-31.
14. Bollard ME, Holmes E, Blackledge CA, Lindon JC, Wilson ID, Nicholson JK. 1H and 19F-NMR spectroscopic studies on the metabolism and urinary excretion of mono- and disubstituted phenols in the rat. Xenobiotica 1996; 26:255-273.
15. Scarfe GB, Wright B, Clayton E, Taylor S, Wilson ID, Lindon JC, Nicholson JK. Quantitative studies on the urinary metabolic fate of 2-chloro-4-trifluoromethylaniline in the rat using 19F NMR spectroscopy and directly coupled HPLC-NMR-MS. Xenobiotica 1999; 29:77-91.
16. Scarfe GB, Lindon JC, Nicholson JK, Wright B, Clayton E, Wilson ID. Investigation of the quantitative metabolic fate and urinary excretion of 3-methyl-4-trifluoromethylaniline and 3-methyl-4-trifluormethylacetanilide in the rat. Drug Metab Dispos 1999; 27:1171-1178.
17. Desmoulin F, Gilard V, Malet-Martino MR, Martino. Metabolism of capecitabine, an oral fluorouracil prodrug: 19F NMR studies in animal models and human urine. Drug Metab Dispos 2002; 30:1221-1229.
18. Tugnait M, Lenz EM, Phillips P, Hofmann M, Spraul M, Lindon JC, Nicholson JK, Wilson ID. The metabolism of 4-trifluoromethoxyaniline and [13C]-4-trifluoromethoxyacetanilide in the rat: detection and identification of metabolites excreted in the urine by NMR and HPLC-NMR. J Pharm Biomed Anal 2002; 28:875-885.
19. Duckett CJ, Wilson ID, Douce DS, Walker HJ, Abou-Shakra FR, Lindon JC, Nicholson JK. Metabolism of 2-fluoro-4-iodoaniline in the earthworm Eisenia veneta using 19F NMR spectroscopy, HPLC-MS, and HPLC-ICPMS (127I). Xenobiotica 2007; 37:1378-1393.
20. Bundy JG, Lenz EM, Osborn D, Weeks JM, Lindon JC, Nicholson JK. Metabolism of 4-fluoroaniline and 4-fluorobiphenyl in the earthworm Eisenia veneta characterised by highresolution NMR spectroscopy with directly coupled HPLC-NMR and HPLC-MS. Xenobiotica 2002; 32:479-470.
21. Lenz EM, Lindon JC, Nicholson JJ, Weeks JM, Osborn D. 19F NMR and directly coupled 19F/1H-HPLC-NMR spectroscopic investigations of the model ecotoxin 3-trifluoromethylaniline in the earthworm species Eisenia veneta. Xenobiotica 2002; 32:535-536.
22. Cloarec O, Dumas ME, Craig A, Barton RH, Trygg J, Hudson J, Blancher C, Gaugier D, Lindon JC, Holmes E, Nicholson JK. Statistical total correlation spectroscopy: an exploratory approach for latent biomarker identification from metabolic 1H NMR data sets. Anal Chem 2005; 77:1282-1289.
23. Holmes E, Loo RL, Cloarec O, Coen M, Tang H, Maibaum E, Bruce S, Chan Q, Elliot P, Stamler J, Wilson ID, Lindon JC, Nicholson JK. Detection of urinary drug metabolite (xenometabolome) signatures in molecular epidemiology studies via statistical total correlation (NMR) spectroscopy. Anal Chem 2007; 79:2629-2640.
24. Keun HC, Athersuch TJ, Beckonert O, Wang Y, Shockcor JP, Wilson ID, Holmes E, Nicholson JK. Heteronuclear (19F-1H) statistical total correlation spectroscopy as a new tool in drug metabolism: a study of flucloxacillin biotransformation. Anal Chem 2008; 80:1073-1079.
25. Everett JR, Jennings K, Woodnutt G. 19F NMR spectroscopy study of the metabolites of flucloxacillin in rat urine. J Pharm Pharmacol 1985; 37:869-873.
26. Crockford DJ, Holmes E, Lindon JC, Plumb RS, Zirah S, Bruce SJ, Rainville P, Stumpf CL, Nicholson JK. Statistical HeterospectroscopY (SHY), a new approach to the integrated analysis of NMR and UPLC-MS datasets: application in metabonomic toxicology studies. Anal Chem 2006; 78:363-371.
27. Lindon JC, Nicholson JK, Wilson ID. Direct coupling of chromatographic separations to NMR spectroscopy. Prog NMR Spectrosc 1996; 29:1-49.
28. Lindon JC, Nicholson JK, Wilson ID. Development of directly-coupled HPLC-NMR and its application to drug metabolism. Drug Metab Rev 1997; 29:705-746.
29. Shockcor JP, Unger SE, Wilson ID, Foxall PJD, Nicholson JK, Lindon JC. Combined hyphenation of HPLC, NMR spectroscopy and ion-trap mass spectrometry (HPLC-NMR-MS) with application to the detection and characterisation of xenobiotic and endogenous metabolites in human urine. Anal Chem 1996; 68:4431-435.
30. Lindon JC, Nicholson JK, Wilson ID. Directly coupled LC-NMR-MS for metabolite identification. Encylopedia of Mass Spectrometry 2007; 8:989-1008.
31. Wilson ID, Th Brinkman UA. Hype and hypernation: multiple hyphenation of column liquid chromatography and spectroscopy. Trends Anal Chem 2007; 26:847-854.
32. Louden D, Handley A, Taylor S, Sinclair I, Lenz E, Wilson ID. High temperature reversedphase HPLC using deuterium oxide as a mobile phase for the separation of model pharmaceuticals with multiple on-line spectroscopic analysis (UV, IR, 1H-NMR and MS). Analyst 2001; 126:1625-1629.
33. Spraul M, Hofmann M, Dvortsack P, Nicholson JK, Wilson ID. Liquid chromatography coupled with high-field proton NMR detection for profiling human urine for endogenous compounds and drug metabolites. J Pharm Biomed Anal 1992; 8:601-605.
34. Spraul M, Hofmann M, Dvortsack P, Nicholson JK, Wilson ID. High-performance liquid chromatography coupled to high-field proton nuclear magnetic resonance spectroscopy: a application to the urinary metabolites of ibuprofen. Anal Chem 1993; 65:327-330.
35. Spraul M, Hofmann M, Wilson ID, Lenz E, Nicholson JK, Lindon JC. Coupling of HLPC with 19F and 1H-NMR spectroscopy to investigate the human urinary excretion of flurbiprofen metabolites. J Pharm Biomed Anal 1993; 11:1004-1015.
36. Farrant RD, Cupid BC, Nicholson JK, Lindon JC. Investigation of the feasibility of directlycoupled HPLC-NMR with 2H detection with application to the metabolism of Ndimethylformamide- d7. J Pharm Biomed Anal 1997; 16:1-5.
37. Lindon JC, Nicholson JK, Wilson ID. Directly-coupled HPLC-NMR and HPLC-NMR-MS in pharmaceutical research and development. J Chromatogr B Biomed Sci Appl 2000; 748:233-258.
38. Clayton E, Taylor S, Wright B, Wilson ID. The application of high performance liquid chromatography, coupled to nuclear magnetic resonance spectroscopy and mass spectrometry (HPLC-NMR-MS), to the characterisation of ibuprofen metabolites from human urine. Chromatographia 1997; 47:264-270.
39. Scarfe GB, Wright B, Clayton E, Taylor S, Wilson ID, Lindon JC, Nicholson JK. 19F-NMR and directly coupled HPLC-NMR-MS investigations into the metabolism of 2-bromo-4-trifluoromethylaniline in the rat: a urinary excretion balance study without the use of radiolabelling. Xenobiotica 1998; 28:373-388.
40. Scarfe GB, Lindon JC, Nicholson JK, Martin P, Wright B, Taylor S, Lenz E, Wilson ID. Investigation of the metabolism of 14C/13C-practolol in rat using directly coupled radio-HPLCNMR-MS. Xenobiotica 2000; 30:717-729.
41. Nicholls AW, Caddick S, Wilson ID, Farrant DR, Lindon JC, Nicholson JK. High resolution NMR spectroscopic studies on the metabolism and futile deacetylation of 4-hydroxyacetanilde (paracetamol) in the rat. Biochem Pharmacol 1995; 49:1155-1164.
42. Nicholls AW, Lindon JC, Farrant RD, Shockcor JP, Wilson ID, Nicholson JK. Directly-coupled HPLC-NMR spectroscopic studies of metabolism and futile deacetylation of phenacetin in the rat. J Pharm Biomed Anal 1999; 20:865-873.
43. Nicholls AW, Farrant RD, Shockor JP, Unger S, Wilson ID, Lindon JC, Nicholson JK. NMR and HPLC-NMR spectroscopic studies of futile deacetylation in paracetamol metabolites in rat and man. J Pharm Biomed Anal 1997; 15:901-910.
44. 3: measurement of futile metabolic deacetylation via HPLC/MS-SPE-NMR and HPLC-ToF MS. Xenobiotica 2006; 36:615-629.
45. Spraul M, Freund AS, Nast RE, Withers RS, Maas WE, Corcoran O. Advancing NMR sensitivity for LC-NMR-MS using a cryoflow probe: application to the analysis of acetaminophen metabolites in urine. Anal Chem 2003; 75:1536-1541.
46. Griffiths L, Horton R. Optimization of LC-NMR. III-Increased signal-to-noise ratio through column trapping. Magn Reson Chem 1998; 36:104-109.
47. Cloarec O, Campbell A, Tseng LH, Braumann U, Spraul M, Scarfe G, Weaver R, Nicholson JK. Virtual chromatographic resolution enhancement in cryoflow LC-NMR experiments via statistical total correlation spectroscopy. Anal Chem 2007; 79:3304-3311.
48. Stachulski AV, Harding JR, Lindon JC, Maggs JL, Park K, Wilson ID. Acyl glucuronides:biological activity, chemical reactivity, and chemical synthesis. J Med Chem 2006; 49:6931-6945.
49. Skordi E, Wilson ID, Lindon JC, Nicholson JK. Kinetic studies on the intramolecular acyl migration of b-1-O-acyl glucuronides: application to the glucuronides of R and S ketoprofen, R and S hydroxy-ketoprofen and tolmetin by 1H NMR spectroscopy. Xenobiotica 2005; 35:715-725.
50. Johnson CH, Wilson ID, Harding JR, Stachulski AV, Iddon L, Nicholson JK, Lindon JC. NMR spectroscopic studies on the in vitro acyl glucuronide migration kinetics of ibuprofen ((þ)-(R, S)-2-(4-isobutylphenyl)propanoic acid), its metabolites and analogues. Anal Chem 2007; 79:8720-8727.
51. Johnson CH, Athersuch TJ, Wilson ID, Meng X, Iddon L, Stachulski AV, Lindon JC, Nicholson JK. Kinetic and J-resolved statistical total correlation NMR spectroscopy (STOCSY) approaches to structural information recovery in complex reacting mixtures: application to acyl glucuronide intramolecular transacylation reactions. Anal Chem 2008; 80:4886-4895.
52. Sidelmann UG, Gavaghan C, Carless HJA, Spraul M, Hofmann M, Lindon JC, Wilson ID, Nicholson JK. 750-MHz directly coupled HPLC-NMR: application to the sequential characterisation of the positional isomers and anomers of 2-, 3-, and 4-fluorobenzoic acid glucuronides in equilibrium mixtures. Anal Chem 1995; 67:4441-4445.
53. Sidelmann UG, Nicholls AW, Meadows PE, Gilbert JW, Lindon JC, Wilson ID, Nicholson JK. High performance liquid chromatography directly coupled to 19F and 1H NMR for the analysis of mixtures of isomeric ester glucuronide conjugates of trifluoromethyl benzoic acids. J Chromatogr 1996; 728:377-385.
54. Sidelmann UG, Hansen SH, Gavaghan C, Carless HJA, Lindon JC, Farrant RD, Wilson ID, Nicholson JK. Measurement of internal acyl migration reaction kinetics using directly coupled HPLC-NMR: application for the positional isomers of synthetic (2-fluorobenzoyl)-Dglucopyranuronic acid. Anal Chem 1996b; 68:2564-2572.
55. Lenz EM, Greatbanks D, Wilson ID, Spraul M, Hofmann M, Troke J, Lindon JC, Nicholson JK. Direct characterisation of drug glucuronide isomers in human urine by HPLC-NMR spectroscopy:application to the positional isomers of 6, 11-dihydro-11-oxidibenz[b, e]oxepin-2-acetic acid glucuronide. Anal Chem 1996; 68:2832-2837.
56. Ruhl R, Thiel R, Lacker TS, Strohschein S, Albert K, Nau H. Synthesis, high-performance liquid chromatography-nuclear magnetic resonance characterization and pharmacokinetics in mice of CD271 glucuronide. J Chromatogr B Biomed Sci Appl 2001; 757:101-109.
57. Akira K, Hasegawa H, Shinohara Y, Imachi M, Hashimoto T. Stereoselective internal acyl migration of 1-beta-O-acyl glucuronides of enantiomeric 2-phenylpropionic acids. Biol Pharm Bull 2000; 23:506-510.
58. Mortensen RW, Corcoran O, Cornett C, Sidelmann UG, Lindon JC, Nicholson JK, Hansen SH. S-Naproxen-b-1-O-acyl glucuronide degradation kinetic studies by stopped-flow high-performance liquid chromatography-1H NMR and high-performance liquid chromatography-UV. Drug Metab Dispos 2001; 29:375-380.
59. Corcoran O, Mortensen RW, Hansen SH, Troke J, Nicholson JK. HPLC/1H NMR spectroscopic studies of the reactive a-1-O-acyl isomer formed during acyl migration of S-naproxen b-1-Oacyl glucuronide. Chem Res Toxicol 2001; 14:1363-1370.
60. Chen W, Shockcor JP, Tonge R, Hunter A, Gartner C, Nelson SD. Protein and nonprotein cysteinyl thiol modification by N-acetyl-p-benzoquinone imine via a novel ipso adduct. Biochemistry 1999; 38:8159.