NMR in Pharmaceutical Science
eMagRes Books Series

NMR in Pharmaceutical Sciences is intended to be a comprehensive source of information for the many individuals that utilize MR in studies of relevance to the pharmaceutical sector. The book is intended to educate and inform those who develop and apply MR approaches within the wider pharmaceutical environment, emphasizing the toolbox that is available to spectroscopists and radiologists.

This book is structured on the key processes in drug discovery, development and manufacture, but underpinned by an understanding of fundamental NMR principles and the unique contribution that NMR (including MRI) can provide. After an introductory chapter, which constitutes an overview, the content is organised into five sections. The first section is on the basics of NMR theory and relevant experimental methods. The rest follow a sequence based on the chronology of drug discovery and development, firstly 'Idea to Lead' then 'Lead to Drug Candidate', followed by 'Clinical Development', and finally 'Drug Manufacture'.  The thirty one chapters cover a vast range of topics from analytical chemistry, including aspects involved in regulatory matters and in the prevention of fraud, to clinical imaging studies.

Whilst this comprehensive volume will be essential reading for many scientists based in pharmaceutical and related industries, it should also be of considerable value to a much wider range of academic scientists whose research is related to the various aspects of pharmaceutical R&D; for them it will supply vital understanding of pharmaceutical industrial concerns and the basis of key decision making processes.

About eMagRes Handbooks

eMagRes (formerly the Encyclopedia of Magnetic Resonance) publishes a wide range of online articles on all aspects of magnetic resonance in physics, chemistry, biology and medicine. The existence of this large number of articles, written by experts in various fields, is enabling the publication of a series of eMagRes Handbooks on specific areas of NMR and MRI. The chapters of each of these handbooks will comprise a carefully chosen selection of eMagRes articles. In consultation with the eMagRes Editorial Board, the eMagRes handbooks are coherently planned in advance by specially-selected Editors, and new articles are written to give appropriate complete coverage. The handbooks are intended to be of value and interest to research students, postdoctoral fellows and other researchers learning about the scientific area in question and undertaking relevant experiments, whether in academia or industry.

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Contributors xi

Series Preface xvii

Preface xix

Part A: Introduction 1

1 Drug Discovery and Development: The Role of NMR
Jeremy R. Everett 3

Part B: NMR Theory & Experimental Methods 21

2 Modern NMR Pulse Sequences in Pharmaceutical R&D
John A. Parkinson 23

3 Experimental NMR Methods for Pharmaceutical Research and Development
Anthony C. Dona 41

4 19F NMR Spectroscopy: Applications in Pharmaceutical Studies
John C. Lindon and Ian D. Wilson 53

5 Quantitative NMR Spectroscopy in Pharmaceutical R&D
Ulrike Holzgrabe 63

6 High-throughput NMR in Pharmaceutical R&D
John C. Hollerton 79

7 Multivariate Data Analysis Methods for NMR-based Metabolic Phenotyping in Pharmaceutical and Clinical Research
Kirill A. Veselkov, James S. McKenzie, and Jeremy K. Nicholson 89

Part C: Idea to Lead 103

8 The Role of NMR in Target Identification and Validation for Pharmaceutical R&D
Krishna Saxena and Harald Schwalbe 105

9 High-resolution MAS NMR of Tissues and Cells
Leo L. Cheng 117

10 NMR Studies of Inborn Errors of Metabolism
Sarantos Kostidis and Emmanuel Mikros 131

11 NMR-based Structure Confirmation of Hits and Leads in Pharmaceutical R&D
Philip J. Sidebottom 147

12 Fragment-based Drug Design Using NMR Methods
Leonor Puchades-Carrasco and Antonio Pineda-Lucena 155

13 Hit Discovery from Natural Products in Pharmaceutical R&D
Olivia Corcoran 173

Part D: Lead to Drug Candidate 183

14 NMR-based Structure Determination of Drug Leads and Candidates
Torren M. Peakman 185

15 Mixture Analysis in Pharmaceutical R&D Using Hyphenated NMR Techniques
Ian D. Wilson and John C. Lindon 197

16 Conformation and Stereochemical Analysis of Drug Molecules
Gary J. Sharman 207

17 NMR Methods for the Assignment of Absolute Stereochemistry of Bioactive Compounds
Jose M. Seco and Ricardo Riguera 221

18 Applications of Preclinical MRI/MRS in the Evaluation of Drug Efficacy and Safety
Thomas M. Bocan, Lauren Keith, and David M. Thomasson 255

19 Practical Applications of NMR Spectroscopy in Preclinical Drug Metabolism Studies
Raman Sharma and Gregory S. Walker 267

20 Preclinical Drug Efficacy and Safety Using NMR Spectroscopy
Muireann Coen and Ian D. Wilson 281

21 Characterization of Pharmaceutical Compounds by Solid-state NMR
Frederick G. Vogt 297

22 Structure-based Drug Design Using NMR
Mark Jeeves, Lee Quill, and Michael Overduin 317

23 Pharmaceutical Technology Studied by MRI
David G. Reid and Stephen J. Byard 331

Part E: Clinical Development 345

24 NMR-based Metabolic Phenotyping for Disease Diagnosis and Stratification
Beatriz Jiménez 347

25 NMR-based Pharmacometabonomics: A New Approach to Personalized Medicine
Jeremy R. Everett 359

26 Clinical MRI Studies of Drug Efficacy and Safety
David G. Reid, Paul D. Hockings, and Nadeem Saeed 373

27 The Role of NMR in the Protection of Intellectual Property in Pharmaceutical R&D
Frederick G. Vogt 385

Part F: Drug Manufacture 395

28 Analysis of Counterfeit Medicines and Adulterated Dietary Supplements by NMR
Myriam Malet-Martino and Robert Martino 397

29 Pharmaceutical Industry: Regulatory Control and Impact on NMR Spectroscopy
Andrea Ruggiero and Sarah K. Branch 413

30 NMR Spectroscopy in the European and US Pharmacopeias
Helen Corns and Sarah K. Branch 425

31 NMR in Pharmaceutical Manufacturing
Edwin Kellenbach and Paulo Dani 441

Index 453

Jeremy R. Everett, Ph.D., Department of Pharmaceutical, Chemical & Environmental Sciences, University of Greenwich, UK

John C. Lindon, Ph.D., Imperial College London, UK

Ian D. Wilson, Ph.D., Imperial College London, UK

Robin Harris, Ph.D., Department of Chemistry, University of Durham, UK