Identification and Determination of Impurities in Drugs (eBook)

S. Gorog (Herausgeber)

eBook Download: PDF

2000 | 1. Auflage
772 Seiten
Elsevier Science (Verlag)
978-0-08-053440-4 (ISBN)

Infos

Impurity profiling is the common name of a group of analytical activities, the aim of which is the detection, identification/structure elucidation and quantitative determination of organic and inorganic impurities, as well as residual solvents in bulk drugs and pharmaceutical formulations. Since this is the best way to characterise the quality and stability of bulk drugs and pharmaceutical formulations, this is the core activity in modern drug analysis.
Due to the very rapid development of the analytical methodologies available for this purpose and the similarly rapid increase of the demands as regards the purity of drugs it is an important task to give a summary of the problems and the various possibilities offered by modern analytical chemistry for their solution. That is the aim of this book.
The book is methodology-oriented. In the first chapter some important aspects of the background of impurity-related analytical studies (toxicological, pharmacopoeial aspects, the characterisation of the sources of impurities and the role of impurity profiling in various fields of drug research, production and therapeutic use) are summarised. Chapter two deals with related organic impurities, the strategies for impurity profiling, the use of chromatographic and related separation methods, spectroscopic, and hyphenated techniques. The subject of the third chapter is the identification and determination of residual solvents. The determination of inorganic impurities is discussed in chapter four. The special problems of degradation products as impurities are dealt with in chapter five. A separate chapter has been compiled to deal with one of the most up-to-date problems in contemporary pharmaceutical analysis, the estimation of enantiomeric purity of chiral drugs. Chapter seven is devoted to various approaches to solve the problem of polymorphic modifications as impurities. Since in the broader sense of the word the microbiological purity of drugs and drug products also belongs to this circle, the most important information from this field is summarised in chapter eight. After the mainly methodology-oriented chapters, the final one concentrates on four groups of drugs (peptides, biotechnological products, antibiotics and steroids) in order to demonstrate the use of the methods described earlier.

Inhalt

Cover 1
Contents 8
Preface 6
List of Contributors 22
Chapter 1. Various aspects of the estimation of impurities in drugs 26
1.1 Introductory remarks 26
1.2 The nature and origin of the impurities in drug substances 34
1.3 Toxicological aspects 48
1.4 The role of impurity profiling in drug research development and production 63
1.5 Regulatory aspects ICH and pharmacopeial perspectives 73
References 90
Chapter 2. Indenification structure elucidation and determination of related organic impurities 92
2.1 Strategies in impurity profiling 92
2.2 UV-VIS spectroscopy and fluorimetry 109
2.3 Mass spectrometry in impurity profiling 122
2.4 NMR spectroscopy 134
2.5 Planar chromatography 171
2.6 Gas chromatography (GC) and related techiniques 208
2.7 High performance liquied chromatography (HPLC) and related techniques 235
2.8 Determination of drug related impurities by capillary electro phoresis 348
2.9 Capillary electrochromatography (CEC) 371
2.10 Supercritical fluid chromatography (SFC) 407
2.11 Purity check by differential scanning calorimetry 421
Reference 424
Chapter 3. Identification and determination of residual solvents 426
3.1 Thrmoanalytical methods 426
3.2 Gas chromatogtraphy and GC/MS 434
3.3 NMR Spectoscopy 466
3.4 Miscellaneous 473
Reference 474
Chapter 4. Identification semiquantitative and quantitative determination of inorganic impurities 475
4.1 Classical methods 475
4.2 Atomic spectroscopy 482
4.3 Other methods 493
Reference 496
Chapter 5. Degradation products as impurities 497
5.1 The relation between drug stability studies and the estimation of impurity profiles 497
5.2 Aims forms and conditions of drug stability testing 501
5.3 Elucidation of degradation pathways 505
5.4 Elucidation of light-induced degradation pathways 522
5.5 Metholological aspects of quantitative drug stability studies based on degradates 531
Reference 547
Chapter 6. Determination of enantiomeric impurities 550
6.1 Introduction 550
6.2 Chromatographic methods 553
6.3 Capillary electrophoretic (CE) methods 565
6.4 Polarimetry ORD and CD spectroscopy 578
6.5 NMR spectroscopy 587
Reference 597
Chapter 7. Estimation of polymorphic midifications as impurities in drugs 600
7.1 The phenomennon and importance of polymorphism 600
7.2 Infrared and Raman spectroscopy 605
7.3 Thermoanalytical methods 617
7.4 X-ray crystallography 626
Reference 631
Chapter 8. Microbiological examination of non-sterile drugs and raw materials 634
8.1 Introductory remarks 634
8.2 Validation 637
8.3 Total viable count 643
8.4 Tests for specified organisms 648
8.5 Concluding remarks 658
Reference 659
Chapter 9. Selected examples (impurity profiling of some groups of drugs 664
9.1 Peptides 664
9.2 Biotechnological products 685
9.3 Antiniotics 709
9.4 Steroids 737
Reference 754
Subject Index 758

Produkt-Details

• Erscheint lt. Verlag: 19.5.2000
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Gesundheitsfachberufe
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
• Themenwelt: Naturwissenschaften ► Chemie ► Analytische Chemie
• Themenwelt: Naturwissenschaften ► Chemie ► Organische Chemie
• Themenwelt: Naturwissenschaften ► Chemie ► Technische Chemie
• Themenwelt: Naturwissenschaften ► Physik / Astronomie
• Themenwelt: Technik ► Elektrotechnik / Energietechnik
• ISBN-10: 0-08-053440-6 / 0080534406
• ISBN-13: 978-0-08-053440-4 / 9780080534404