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E-raamat: NMR Spectroscopy in Drug Development and Analysis [Wiley Online]

(Spectral Service, Köln, Ge), (Medical Academy, Warsaw, Poland), (Pharmazeutisches Institut, Universität Bonn, Ge)
  • Formaat: 312 pages
  • Ilmumisaeg: 10-Sep-1999
  • Kirjastus: Blackwell Verlag GmbH
  • ISBN-10: 3527613641
  • ISBN-13: 9783527613649
  • Wiley Online
  • Hind: 163,88 €*
  • * hind, mis tagab piiramatu üheaegsete kasutajate arvuga ligipääsu piiramatuks ajaks
  • Formaat: 312 pages
  • Ilmumisaeg: 10-Sep-1999
  • Kirjastus: Blackwell Verlag GmbH
  • ISBN-10: 3527613641
  • ISBN-13: 9783527613649
Since the development of the NMR spectrometer in the 1950s, NMR spectra have been widely used for the elucidation of the 2D structure of newly synthesized and natural compounds. In the 1980s, the high-resolution NMR spectrometer (> 300 Mhz) and 2D experiments were introduced, which opens up the possibility to determine the 3D structure of large molecules, especially biomolecules. However, NMR spectroscopy has been rarely applied to drug analysis.
This book illustrates the power and versatility of NMR spectroscopy in the determination of impurities in and the content of drugs, the composition of polymer excipients, the characterization of isomeric drug mixtures, the complexity of drugs with small-size components or ions, and the behavior of drugs in acid and basic solution. In addition, NMR spectroscopy and especially the hyphenated technique with HPLC is shown to be a powerful tool to measure a drug and its metabolites in various body fluids. The solid state NMR technique can give information on the structure, especially the conformation of drugs and excipients in drug formulations. Recently, SAR by NMR, introduced by Fesik, impressively demonstrated the potential of NMR spectroscopy in drug development and in the characterization of the interaction between large molecules and ligands. The complexation between proteins, lipids and cyclodextrins with drugs is described. Finally, NMR imaging (MRI and MRS) can be used to characterize the liberation of drugs from a drug formulation. Furthermore, the distribution of substances in plants, in animals, in tissues and in humans can be visualized by imaging.
In short, this book covers all aspects of drug analysis.
Preface Contributors Introduction 1(4) B. W. K. Diehl The Instrument 2(1) Principles 2(2) Spectra 2(1) Response 3(1) Reproducibility 3(1) Calibration 3(1) Experimental 4(1) NMR Spectroscopy in the European Regulatory Dossier 5(11) S. Branch Directives, Rules and Guidelines 5(1) Information Required to Establish Quality 6(2) Control of Starting Materials 8(5) Specifications and Routine Tests 8(2) Scientific Data 10(3) Control of the Finished Product 13(1) Stability Studies 14(1) Concluding Remarks 15(1) Analysis of Drugs 16(45) B. W. K. Diehl U. Holzgrabe NMR Spectroscopy in International Pharmacopoeias and Related Applications 16(16) Polymers 22(4) Biomolecules 26(6) Identification and Quantification of Impurities in Drugs 32(11) Impurities Resulting from the Synthesis Pathway 32(4) Decomposition Reactions 36(7) Quantification of Drugs in Dosage Forms 43(6) Analysis of Single Drugs in Dosage Forms 43(2) Analysis of Drug Mixtures in Dosage Forms 45(3) Analysis of Drugs and Decomposition or Isomer Traces in Dosage Forms 48(1) Analysis of Complex Mixtures, e. g. Excipients 49(8) Phospholipids 50(2) Silicones 52(3) Fluorine Containing Substances 55(2) Concluding Remarks 57(4) pH-Dependent NMR Measurements 61(16) G. Hagele U. Holzgrabe Introduction 61(1) Determination of the Site of Protonation 62(3) Determination of Dissociation Constants and Stability Constants by NMR-Controlled Titrations 65(3) Applications in Pharmacy 68(9) Macroscopic Dissociation Equilibria 68(1) Microscopic Dissociation Equilibria 69(8) Complexation Behaviour of Drugs Studied by NMR 77(5) B. W. K. Diehl U. Holzgrabe Selfassociation of Drugs and Association with Other Components of a Formulation 77(1) Complexation with Cations 78(4) Determination of the Isometric Composition of Drugs 82(19) B. W. K. Diehl U. Holzgrabe Determination of the Enantiomeric Excess 85(2) Comparison of Different CSAs 87(14) On-line Coupling of HPLC or SFC 101(17) K. Albert Introduction 101(3) HPLC-NMR Coupling 104(5) Continuous-flow Measurements 104(3) Stopped-flow Measurements 107(2) SPE-HPLC-NMR Coupling 109(2) SFE-NMR and SFC-NMR Coupling 111(2) Capillary Separations 113(5) NMR of Body Fluids 118(16) U. Holzgrabe NMR of Urine-Studies of Metabolism 118(7) 1H NMR Spectroscopy 118(4) 19F NMR Spectroscopy 122(2) 15N NMR Spectroscopy 124(1) 31P NMR Spectroscopy 124(1) NMR of Bile, Blood Plasma, Cerebrospinal and Seminal Fluids 125(3) LC NMR Hyphenation 128(6) NMR as a Tool in Drug Research 134(20) G. Gemmecker Introduction 134(1) Protein Structures from NMR 135(1) Protein-Ligand Interactions 136(18) NMR of Molecular Complexes 136(1) Aspects of Binding Affinity 137(2) Exchange Time Scales for NMR Parameters 139(1) Transfer NOE 140(2) Isotope Filters 142(2) Measuring Binding Affinities by NMR 144(3) Binding Site Localization 147(2) Solvent-Accessible Surfaces 149(1) Screening Protein-Ligand Interactions 149(2) Conclusion 151(3) Ligand-Cyclodextrin complexes 154(20) B. Chankvetadze G. Blaschke G. Pintore Introduction 154(1) Cyclodextrins and their Properties 155(2) Application of Cyclodextrins in Drug Development and Drug Analysis 157(2) NMR Spectroscopic Studies of Ligand-CD Complexes 159(15) Stoichiometry of Ligand-CD Complexes 159(5) Binding Constants of Ligand-CD Complexes 164(2) Structure and Dynamics of Ligand-CD Complexes 166(8) Ligand-Membrane Interaction 174(57) J. K. Seydel Introduction 174(1) Functioning, Composition and Organization of Membranes 174(16) The Physiology of Cells and the Importance of Membranes for their Functioning 174(1) Composition and Organization of Membranes 175(1) Mammal Membranes 175(8) Artificial Membranes and Liposome Preparation 183(1) Dynamic Molecular Organisation of Membranes 184(1) Thermotropic and Lysotropic Mesomorphism of Phospholipids 185(1) Phase separation and domain formation 186(1) Possible Effects of Drugs on Membranes and Effects of Membranes on Drugs 187(3) NMR Spectrometry; and Analytical Tool for the Study and Quantification of Ligand-Membrane Interactions 190(36) Tools for the Analysis and Quantification of Drug-Membrane Interactions 190(2) Study of Membrane Polymorphism by 31+P-NMR 192(2) Effect of Cholesterol and Diacylglycerols 194(1) Effect of Drugs 195(1) 31P-NMR to Study Changes in Orientation of Phospholipid Head Groups 196(3) 31P NMR to Study Drug Transmembrane Transport 199(4) 1H-NMR in Combination with Pr3+ fot the Studying of Drug-Location 203(3) The Use of 2H-NMR and 13C-NMR to Determine the Degree of Order and the Molecular Dynamics of Membranes 206(2) Change in Relaxation Rate 1/T2; a Method of Quantifying Drug-Membrane Interaction 208(9) NOE-NMR in the Study of Membrane Induced Changes in Drug Conformation 217(3) Combination of Methods and Techniques for the Studying of Drug-Membrane Interactions 220(6) Concluding remarks 226(5) Solid-State NMR in Drug Analysis 231(26) I. Wawer Fundamentals and Techniques of Solid State NMR 231(10) Solid State Conformations of Drugs and Biologically Active Molecules 241(4) Polymorphism/Pseudopolymorphism of Drugs 245(7) Studies of Tablets and Excipients 252(5) MR Imaging and MR Spectroscopy 257(37) I. Wawer In vitro and in vivo Measurement Methods 257(4) 1H MR Imaging of Tablets 261(4) 1H Imaging of Plants 265(4) Studies on Biopsy Samples and Tissues 269(4) Multinuclear Preclinical Measurements in Animals 273(4) MRI and MRS in Humans 277(17) Studies of brain 277(6) MR Imaging of Breast 283(1) Musculoskeletal Tumors 284(2) Other Studies 286(8) Concluding remarks 294 U. Holzgrabe
Ulrike Holzgrabe and Iwona Wawer are the authors of NMR Spectroscopy in Drug Development and Analysis, published by Wiley.