Nhóm I: Các kỹ thuật phổ và quang phổ

1. Quang phổ UV / Vis và ảnh UV

2. Phổ huỳnh quang (Fluorescence Spectroscopy)
3. Phổ hồng ngoại trung và gần
4. Phổ Raman
5. Phổ và ảnh Terahertz Dược phẩm (Pharmaceutical Terahertz
Spectroscopy and Imaging)
6. Phổ quay chiều vòng cho việc xác định cấu trúc protein (Circular
Dichroism Spectroscopy for Structural Characterization of Proteins)
7. Ứng dụng của phổ khối trong khoa học phát triển thuốc
Nhóm II: Diffractometric Techniques
8. An Overview of Powder X-ray Diffraction
and Its Relevance to Pharmaceutical Crystal Structures
9. Single-Crystal X-ray Diffraction
10. Applications of Small Angle X-ray Scattering in Pharmaceutical Science
Nhóm III: Thermal Techniques
11. Thermal Analysis of Pharmaceuticals
12. Isothermal Microcalorimetry
Nhóm IV: Separation Techniques
13. HPLC/UHPLC
14. Capillary-Based Techniques for Physical-Chemical
Characterization of Drug Substances and Drug Delivery Systems
15. Asymmetrical Flow Field Flow Fractionation: A Useful Tool for the
Separation of Protein Pharmaceuticals and Particulate Systems
Nhóm V: Imaging Techniques
16. Light and Electron Microscopy
 17. Vibrational Spectroscopic Imaging
18. Magnetic Resonance Imaging and Its Applications to Solid
Pharmaceutical Dosage Forms
19. Mass Spectrometry Imaging of Pharmaceuticals: From Tablets to
Tissues
20. Applications of AFM in Pharmaceutical Sciences
Nhóm VI: Techniques to Characterize Particles
21. Particle Size Analysis of Micro and Nanoparticles
22. Particle Size Measurements in Aerosols
Nhóm VII: Rheological Techniques
23. Rheology in Pharmaceutical Sciences
Nhóm VIII: Release and Uptake Testing Techniques
24. Evaluating Oral Drug Delivery Systems: Dissolution Models
25. Evaluating Oral Drug Delivery Systems: Digestion Models
26. Application of Cell Culture and Tissue Models for Assessing Drug
Transport

1. Control of the quality of analytical methods 1

Introduction 1
Control of errors in analysis 2
Accuracy and precision 5
Validation of analytical procedures 7
Standard operating procedure (SOP) for the assay of paracetamol tablets 10
Compound random errors 11
Reporting of results 13
Other terms used in the control of analytical procedures 14
Basic calculations in pharmaceutical analysis 19
Additional problems 24
2. Physical and chemical properties of drug molecules 26
Introduction 26
Calculation of pH value of aqueous solutions of strong and weak
acids and bases 27
Acidic and basic strength and pKa 29
Henderson–Hasselbalch equation 29
Ionisation of drug molecules 31
Buffers 33
Salt hydrolysis 36
Activity, ionic strength and dielectric constant 37
Partition coefficient 38
Drug stability 41
Stereochemistry of drugs 43
Measurement of optical rotation 49
Profiles of physico-chemical properties of some drug molecules 50
Additional problems 57
3. Titrimetric and chemical analysis methods 60
Keypoints 60
Introduction 61
Instrumentation and reagents 61
Direct acid/base titrations in the aqueous phase 62
Titrations of the salts of weak bases in mixed aqueous/non-aqueous media 65
Indirect titrations in the aqueous phase 66
Non-aqueous titrations 68
Argentimetric titrations 70
Compleximetric titrations 70
Redox titrations 71
Iodometric titrations 73
Ion pair titrations 75
Diazotisation titrations 76
Potentiometric titrations 77
Karl Fischer titration (coulometric end-point detection) 81
Automation of wet chemical methods 82
Applications of FIA in pharmaceutical analysis 84
Additional problems 87
4. Ultraviolet and visible spectroscopy 90
Keypoints 90
Introduction 91
Factors governing absorption of radiation in the UV/visible region 92
Beer–Lambert Law 94
Instrumentation 95
Diode array instruments 96
Instrument calibration 96
UV spectra of some representative drug molecules 98
Use of UV/visible spectrophotometry to determine pKa values 102
Applications of UV/visible spectroscopy to pharmaceutical quantitative
analysis 103
Difference spectrophotometry 107
Derivative spectra 109
Applications of UV/visible spectroscopy in preformulation and
formulation 112
Additional problems 113
5. Infrared spectrophotometry 115
Keypoints 115
Introduction 116
Factors determining intensity and energy level of absorption in IR spectra 117
Instrumentation 118
Sample preparation 120
Application of IR spectrophotometry in structure elucidation 123
Examples of IR spectra of drug molecules 124
IR spectrophotometry as a fingerprint technique 127
Infrared spectrophotometry as a method for identifying polymorphs 130
Near-infrared analysis (NIRA) 130
Keypoints 130
Introduction 131
Examples of NIRA applications 131
Additional problems 135
6. Atomic spectrophotometry 138
Atomic emission spectrophotometry (AES) 138
Keypoints 138
Introduction 138
Instrumentation 139
viii Pharmaceutical analysis
Examples of quantitation by AES 140
Interferences in AES analysis 142
Assays based on the method of standard additions 143
Atomic absorption spectrophotometry (AAS) 145
Keypoints 145
Introduction 145
Instrumentation 146
Examples of assays using AAS 146
Some examples of limit tests employing AAS 148
Inductively coupled plasma emission spectroscopy 150
7. Molecular emission spectroscopy 152
Fluorescence spectrophotometry 152
Keypoints 152
Introduction 153
Instrumentation 154
Molecules which exhibit fluorescence 154
Factors interfering with fluorescence intensity 155
Applications of fluorescence spectrophotometry in pharmaceutical
analysis 156
Raman spectroscopy 159
Keypoints 159
Introduction 160
Instrumentation 161
Applications 161
8. Nuclear magnetic resonance spectroscopy 165
Keypoints 165
Introduction 166
Instrumentation 167
Proton (1
H) 168
Application of NMR to structure confirmation in some drug molecules 188
Carbon NMR 192
Two-dimensional NMR spectra 194
Application of NMR to quantitative analysis 199
Other specialised applications of NMR 200
9. Mass spectrometry 204
Keypoints 204
Introduction 205
Ion generation 205
Other ionisation methods 214
Ion separation techniques 215
A more detailed consideration of mass spectra 219
Molecular fragmentation patterns 220
Gas chromatography–mass spectrometry (GC–MS) 231
Applications of GC–MS with EI 232
Contents ix
Tandem mass spectrometry 236
High-resolution mass spectrometry 244
Mass spectrometry of proteins 246
Mass spectrometry in drug discovery 248
10. Chromatographic theory 252
Introduction 252
Void volume and capacity factor 252
Calculation of column efficiency 253
Origins of band broadening in HPLC 254
Parameters used in evaluating column performance 258
Data acquisition 262
Report generation 263
11. Gas chromatography 265
Keypoints 265
Introduction 266
Instrumentation 266
Selectivity of liquid stationary phases 272
Use of derivatisation in GC 280
Summary of parameters governing capillary GC performance 283
GC detectors 284
Applications of GC in quantitative analysis 284
Determination of manufacturing and degradation residues by GC 291
Determination of residual solvents 294
Solid-phase microextraction (SPME) 297
Applications of GC in bioanalysis 298
Additional problems 299
12. High-performance liquid chromatography 301
Keypoints 302
Introduction 302
Instrumentation 302
Stationary and mobile phases 303
Structural factors which govern rate of elution of compounds from HPLC
columns 306
More advanced consideration of solvent selectivity in reverse-phase
chromatography 313
Effect of temperature on HPLC 316
Summary of stationary phases used in HPLC 317
A more advanced consideration of reverse-phase stationary phases 320
Summary of detectors used in HPLC 322
Performance of a diode array detector 323
Applications of HPLC to the quantitative analysis of drugs in formulations 327
Assays involving more specialised HPLC techniques 340
Additional problems 355
x Pharmaceutical analysis
13. Thin-layer chromatography 358
Keypoints 358
Introduction 359
Instrumentation 359
TLC chromatogram 360
Stationary phases 361
Elutropic series and mobile phases 361
Modification of TLC adsorbant 365
Detection of compounds on TLC plates following development 366
Applications of TLC analysis 367
High-performance TLC (HPTLC) 372
14. High-performance capillary electrophoresis 376
Keypoints 376
Introduction 377
Instrumentation 380
Control of separation 382
Applications of CE in pharmaceutical analysis 384
Use of additives in the running buffer 388
Additional problems 396
15. Extraction methods in pharmaceutical analysis 398
Keypoints 398
Introduction 399
Commonly used excipients in formulations 399
Tablets and capsules 399
Solvent extraction methods 400
Microdialysis extraction 404
Solid-phase extraction (SPE) 404
Keypoints 404
Introduction 405
Methodology 405
Types of adsorbants used in SPE 407
Typical extraction methodologies using lipophilic silica gels 408
Adaptation of SPE for automated on-line extraction prior to HPLC analysis 413
Recent developments in solid-phase and on-line extraction 41