Handbook of Isolation and Characterization of Impurities in Pharmaceuticals
Regular price
124.000 KD
inc. VAT
Couldn't load pickup availability
Table of contents
- Title Pageiii
- Copyright Pageiv
- CONTENTSv
- PREFACExi
- Contributorsxv
- Chapter 1. Overview: Isolation and Characterization of Impurities1
- I. Introduction1
- II. Designations of Impurities4
- III. Regulatory Requirements7
- IV. Sources of Impurities8
- V. Analytical Method Development14
- VI. Isolation Methods18
- VII. Characterization Methods20
- VIII. Case Studies22
- IX. Summary24
- References24
- Chapter 2. Review of Regulatory Guidance on Impurities27
- I. Introduction27
- II. Types of Impurities„Drug Substance28
- III. Role of Compendia30
- IV. Role of Drug Master Files (DMF)„Type II and Impurities Evaluation31
- V. Reference Standards for the Quantitation of Impurities and Analytical Procedures32
- VI. Qualification of Impurities and New Impurities32
- VII. Impurities in Drug Products33
- VIII. Analytical Methodology for Impurities in Drug Product33
- IX. Impurities Quantitation Post-Approval36
- X. Role of Sponsors36
- XI. Summary36
- References37
- Chapter 3. Polymorphic and Solvatomorphic Impurities39
- I. Introduction39
- II. X-ray Diffraction40
- III. Thermal Methods of Analysis44
- IV. Vibrational Spectroscopy49
- V. Solid-State Nuclear Magnetic Resonance Spectrometry57
- References69
- Chapter 4. Impurities in Drug Products75
- I. Introduction75
- II. Water76
- III. Peroxides78
- IV. Aldehydes79
- V. Metal Impurities80
- VI. Small Molecule Carboxylic Acids82
- VII. Leachables/Extractables82
- VIII. Alcohols as Impurities83
- IX. Biological Impurities83
- X. Additives in Excipients84
- XI. Final Observations85
- XII. Summary85
- References85
- Chapter 5. Strategies for Investigation and Control of Process- and Degradation-Related Impurities89
- I. Introduction89
- II. Goals and Strategies91
- III. Process-Related Impurities95
- IV. Degradation-Related Impurities102
- V. Summary and Conclusions115
- References116
- Chapter 6. Reference Standards119
- I. Introduction119
- II. Definitions120
- III. Life Cycle121
- IV. Governance125
- V. Qualification Process127
- VI. Summary139
- References139
- Chapter 7. Sample Selection for Analytical Method Development145
- I. Introduction145
- II. Components of the Key Predictive Sample Set (KPSS)147
- III. Stereoisomers147
- IV. Matrix Components150
- V. Process-Related Impurities (PRIs)150
- VI. Purposeful Degradation Samples152
- VII. Stability Samples155
- VIII. Phase-Solubility Analysis156
- IX. Sample Selection Strategies159
- X. Summary162
- Glossary162
- References163
- Chapter 8. Sample Preparation Methods for the Analysis of Pharmaceutical Materials165
- I. Introduction166
- II. Solid-Phase Extraction (SPE)166
- III. Liquid–Liquid Extraction (LLE)174
- IV. Supercritical Fluid Extraction (SFE)181
- V. Accelerated Solvent Extraction (ASE)189
- VI. Centrifugation194
- VII. Filtration195
- VIII. Summary199
- References199
- Chapter 9. Isolation Methods I: Thin-Layer Chromatography203
- I. Introduction to Thin-Layer Chromatography (TLC)203
- II. TLC Applications in Pharmaceutical Industry206
- III. TLC Method Development and Validation207
- IV. Impurity Isolation and Characterization by TLC221
- References228
- Chapter 10. Isolation Methods II: Column Chromatography231
- I. Introduction231
- II. Background232
- III. Stationary Phases233
- IV. Equipment237
- V. Screening240
- VI. Development of Preparative Method244
- VII. Scaleup of Preparative Method246
- Summary248
- References248
- Chapter 11. Mass Spectral Characterization249
- I. Introduction249
- II. Relevance of Impurity Characterization252
- III. The coupling of Liquid-Phase Separations and Mass Spectrometers259
- IV. Ion Formation264
- V. Analyzers273
- VI. Ion Structure Interrogation277
- VII. Data Acquisition and Interpretation282
- VIII. Applications286
- IX. Conclusions288
- X. Summary289
- References290
- Chapter 12. NMR Characterization of Impurities301
- I. Introduction to Nuclear Magnetic Resonance (NMR)301
- II. Information Gathering304
- III. Sample Preparation for NMR305
- IV. Sample Preparation for LC-NMR307
- V. NMR Instrumentation309
- VI. NMR Experiments314
- VII. Choosing an Experiment Set324
- VIII. Data Interpretation325
- IX. Final Steps334
- X. Summary336
- References337
- Chapter 13. Hyphenated Characterization Techniques341
- I. Introduction341
- II. Experimental Examples350
- III. Conclusions356
- References357
- Chapter 14. Solving Impurity/Degradation Problems: Case Studies361
- I. Introduction and Background361
- II. Case Studies368
- III. Summary and Conclusions398
- Appendix„Lessons Learned398
- References399
- Index401
The United States Food and Drug Administration (FDA) and other regulatory bodies around the world require that impurities in drug substance and drug product levels recommended by the International Conference on Harmonisation (ICH) be isolated and characterized.
Identifying process-related impurities and degradation products also helps us to understand the production of impurities and assists in defining degradation mechanisms. When this process is performed at an early stage, there is ample time to address various aspects of drug development to prevent or control the production of impurities and degradation products well before the regulatory filing and thus assure production of a high-quality drug product.
This book, therefore, has been designed to meet the need for a reference text on the complex process of isolation and characterization of process-related (synthesis and formulation) impurities and degradation products to meet critical requlatory requirements.
It's objective is to provide guidance on isolating and characterizing impurities of pharmaceuticals such as drug candidates, drug substances, and drug products. The book outlines impurity identification processes and will be a key resource document for impurity analysis, isolation/synthesis, and characterization.
- Provides valuable information on isolation and characterization of impurities.
- Gives a regulatory perspective on the subject.
- Describes various considerations involved in meeting regulatory requirements.
- Discusses various sources of impurities and degredation products.
Identifying process-related impurities and degradation products also helps us to understand the production of impurities and assists in defining degradation mechanisms. When this process is performed at an early stage, there is ample time to address various aspects of drug development to prevent or control the production of impurities and degradation products well before the regulatory filing and thus assure production of a high-quality drug product.
This book, therefore, has been designed to meet the need for a reference text on the complex process of isolation and characterization of process-related (synthesis and formulation) impurities and degradation products to meet critical requlatory requirements.
It's objective is to provide guidance on isolating and characterizing impurities of pharmaceuticals such as drug candidates, drug substances, and drug products. The book outlines impurity identification processes and will be a key resource document for impurity analysis, isolation/synthesis, and characterization.
- Provides valuable information on isolation and characterization of impurities.
- Gives a regulatory perspective on the subject.
- Describes various considerations involved in meeting regulatory requirements.
- Discusses various sources of impurities and degredation products.