Additional Information
Book Details
Abstract
Pharmaceutical analysis determines the purity, concentration, active compounds, shelf life, rate of absorption in the body, identity, stability, rate of release etc. of a drug. Testing a pharmaceutical product involves a variety of chemical, physical and microbiological analyses. It is reckoned that over £10 billion is spent annually in the UK alone on pharmaceutical analysis, and the analytical processes described in this book are used in industries as diverse as food, beverages, cosmetics, detergents, metals, paints, water, agrochemicals, biotechnological products and pharmaceuticals.
This is the key textbook in pharmaceutical analysis, now revised and updated for its fourth edition.
- Worked calculation examples
- Self-assessment
- Additional problems (self tests)
- Practical boxes
- Key points boxes
- New chapter on Biotech products.
- New chapter on electrochemical methods in diagnostics.
- Greatly extended chapter on molecular emission spectroscopy to accommodate developments and innovations in the area.
- Now on StudentConsult
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| IFC_StudentConsult | IFC2 | ||
| Pharmaceutical Analysis | i | ||
| Copyright Page | iv | ||
| Preface | v | ||
| Table Of Contents | vii | ||
| Learning resources | xiii | ||
| 1 Control of the quality of analytical methods | 1 | ||
| Introduction | 1 | ||
| Control of errors in analysis | 2 | ||
| Accuracy and precision | 4 | ||
| Validation of analytical procedures | 7 | ||
| The analytical procedure | 7 | ||
| Levels of precision | 7 | ||
| Repeatability | 8 | ||
| Intermediate precision | 10 | ||
| Reproducibility | 10 | ||
| Accuracy | 10 | ||
| Standard operating procedure (SOP) for the assay of paracetamol tablets | 11 | ||
| Compound random errors | 11 | ||
| Reporting of results | 13 | ||
| Other terms used in the control of analytical procedures | 14 | ||
| System suitability | 14 | ||
| Analytical blank | 14 | ||
| Calibration | 14 | ||
| Limit of detection | 14 | ||
| Limit of quantification | 15 | ||
| Linearity | 15 | ||
| Range | 17 | ||
| Robustness | 18 | ||
| Selectivity | 18 | ||
| Sensitivity | 18 | ||
| Weighing by difference | 19 | ||
| Basic calculations in pharmaceutical analysis | 19 | ||
| Percentage volume/volume (%v/v) | 20 | ||
| Percentage weight in volume (%w/v) | 20 | ||
| Dilutions | 20 | ||
| Preparation of standard stock solutions | 21 | ||
| Percentage weight/weight (%w/w) | 22 | ||
| Parts per million (ppm) calculations | 23 | ||
| Working between weights and molarity | 23 | ||
| Definitions | 23 | ||
| References | 25 | ||
| Further reading | 25 | ||
| 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 | ||
| Dissociation of water | 27 | ||
| Strong acids and bases | 27 | ||
| Weak acids and bases | 27 | ||
| Acidic and basic strength and pKa | 29 | ||
| Henderson–Hasselbalch equation | 29 | ||
| Ionisation of drug molecules (see Animation 2.1) | 30 | ||
| Diphenhydramine | 31 | ||
| Ibuprofen | 31 | ||
| Buffers | 32 | ||
| Salt hydrolysis | 36 | ||
| Activity, ionic strength and dielectric constant | 36 | ||
| Partition coefficient | 38 | ||
| Effect of pH on partitioning (see Animation 2.1) | 39 | ||
| Drug stability | 41 | ||
| Zero-order degradation | 42 | ||
| First-order degradation | 42 | ||
| Stereochemistry of drugs | 43 | ||
| Geometrical isomerism | 44 | ||
| Chirality and optical isomerism | 44 | ||
| Diastereoisomers | 47 | ||
| Measurement of optical rotation (see Animation 2.3) | 48 | ||
| Profiles of physico-chemical properties of some drug molecules | 50 | ||
| Procaine | 50 | ||
| Paracetamol | 50 | ||
| Aspirin | 51 | ||
| Benzylpenicillin | 51 | ||
| 5-Fluorouracil | 52 | ||
| Acebutolol | 53 | ||
| Sulfadiazine | 53 | ||
| Isoprenaline | 54 | ||
| Prednisolone | 54 | ||
| Guanethidine | 55 | ||
| Pyridostigmine bromide | 55 | ||
| References | 57 | ||
| Further reading | 57 | ||
| 3 Titrimetric and chemical analysis methods | 58 | ||
| Introduction | 59 | ||
| Instrumentation and reagents | 59 | ||
| Glassware | 59 | ||
| Primary standards and standard solutions | 59 | ||
| Direct acid/base titrations in the aqueous phase | 60 | ||
| Strong acid/strong base titrations | 60 | ||
| Weak acid/strong base and weak base/strong acid titrations (see Animation 3.2) | 61 | ||
| Titrations of the salts of weak bases in mixed aqueous/non-aqueous media | 63 | ||
| Indirect titrations in the aqueous phase | 64 | ||
| Estimation of esters by back titration | 64 | ||
| Saponification value (see Animation 3.3) | 64 | ||
| Estimation of alcohols and hydroxyl values by reaction with acetic anhydride (AA) | 65 | ||
| Non-aqueous titrations | 66 | ||
| Theory | 66 | ||
| Non-aqueous titration of weak bases | 67 | ||
| Non-aqueous titration of weak acids | 68 | ||
| Argentimetric titrations | 68 | ||
| Compleximetric titrations | 68 | ||
| Redox titrations | 69 | ||
| Theory | 69 | ||
| Iodometric titrations | 71 | ||
| Direct titrations | 71 | ||
| Iodine displacement titrations | 72 | ||
| Iodine-absorbing substances in penicillins | 73 | ||
| Ion pair titrations | 73 | ||
| Titrations using indicator dyes | 74 | ||
| Titrations using iodide as a lipophilic anion | 74 | ||
| Diazotisation titrations | 74 | ||
| Potentiometric titrations | 75 | ||
| Potentiometric end-point detection | 75 | ||
| Use of potentiometric titration to determine pKa values (see Animation 3.4) | 77 | ||
| Karl Fischer titration (coulometric end-point detection) | 78 | ||
| Automation of wet chemical methods | 80 | ||
| Automatic titration (Fig. 3.21) | 80 | ||
| Flow injection analysis | 81 | ||
| Applications of FIA in pharmaceutical analysis | 82 | ||
| Determination of chloroxine | 82 | ||
| Determination of captopril | 83 | ||
| Determination of non-steroidal anti-inflammatory drugs | 83 | ||
| Determination of promethazine | 83 | ||
| Determination of chlorocresol | 83 | ||
| Limit test for heavy metals | 83 | ||
| Use of segmented flow in determination of partition coefficients | 84 | ||
| Automated dissolution testing | 84 | ||
| References | 87 | ||
| Further reading | 87 | ||
| 4 Ultraviolet and visible spectroscopy | 88 | ||
| Introduction | 89 | ||
| Factors governing absorption of radiation in the UV/visible region (see Animation 4.1 and Animation 4.2) | 90 | ||
| Beer–Lambert Law | 92 | ||
| Instrumentation | 93 | ||
| Diode array instruments | 93 | ||
| Instrument calibration | 94 | ||
| Calibration of absorbance scale | 94 | ||
| Calibration of wavelength scale | 95 | ||
| Determination of instrumental resolution | 95 | ||
| Determination of stray light | 95 | ||
| UV spectra of some representative drug molecules | 96 | ||
| Steroid enones | 96 | ||
| Ephedrine: the benzoid chromophore | 96 | ||
| Ketoprofen: extended benzene chromophore | 97 | ||
| Procaine: amino group auxochrome | 97 | ||
| Phenylephrine: hydroxyl group auxochrome | 98 | ||
| Use of UV/visible spectrophotometry to determine pKa values | 99 | ||
| Applications of UV/visible spectroscopy to pharmaceutical quantitative analysis | 100 | ||
| Assay examples | 101 | ||
| Furosemide (frusemide) in tablet form | 101 | ||
| Assay of cyclizine lactate in an injection | 101 | ||
| Assay of penicillins by derivatisation (Fig. 4.12) | 103 | ||
| Assay of adrenaline in lidocaine (lignocaine) adrenaline injection | 104 | ||
| Difference spectrophotometry | 105 | ||
| Analysis of aspirin in dextropropoxyphene compound tablets | 105 | ||
| Derivative spectra | 106 | ||
| Applications of UV/visible spectroscopy in preformulation and formulation | 109 | ||
| Partition coefficient | 109 | ||
| Solubility | 110 | ||
| Release of a drug from a formulation | 110 | ||
| Reference | 112 | ||
| Further reading | 112 | ||
| 5 Infrared spectrophotometry | 113 | ||
| Introduction | 114 | ||
| Factors determining intensity and energy level of absorption in IR spectra | 115 | ||
| Intensity of absorption | 115 | ||
| Energy level of absorption | 116 | ||
| Instrumentation | 116 | ||
| Instrument calibration | 118 | ||
| Sample preparation | 118 | ||
| Application of IR spectrophotometry in structure elucidation | 121 | ||
| Examples of IR spectra of drug molecules | 122 | ||
| IR spectrophotometry as a fingerprint technique | 125 | ||
| Preparation of samples for fingerprint determination | 125 | ||
| Infrared spectrophotometry as a method for identifying polymorphs | 128 | ||
| Near-infrared analysis (NIRA) | 128 | ||
| Introduction | 129 | ||
| Examples of NIRA applications | 129 | ||
| Determination of particle size in United States Pharmacopoeia (USP) grade aspirin | 130 | ||
| Determination of blend uniformity | 130 | ||
| Determination of active ingredients in multicomponent dosage forms | 131 | ||
| In-pack determination of active ingredients | 131 | ||
| Determination of polymorphs | 131 | ||
| Moisture determination | 132 | ||
| Process control of components in a shampoo | 132 | ||
| References | 134 | ||
| Further reading | 134 | ||
| Additional reading | 135 | ||
| 6 Atomic spectrophotometry | 136 | ||
| Atomic emission spectrophotometry (AES) | 136 | ||
| Introduction | 136 | ||
| Instrumentation | 137 | ||
| Examples of quantitation by AES | 138 | ||
| Assay of sodium and potassium ions in an i.v. infusion | 138 | ||
| Interferences in AES analysis (see Animation 6.3) | 140 | ||
| Ionisation | 140 | ||
| Viscosity | 140 | ||
| Anionic interference | 140 | ||
| Assays based on the method of standard additions | 141 | ||
| Assay for KCl, NaCl and glucose i.v. infusion | 141 | ||
| Atomic absorption spectrophotometry (AAS) | 143 | ||
| Introduction | 143 | ||
| Instrumentation | 144 | ||
| Examples of assays using AAS (see Animation 6.4) | 144 | ||
| Assay of calcium and magnesium in haemodialysis fluid | 144 | ||
| Some examples of limit tests employing AAS | 146 | ||
| Assay of lead in sugars | 146 | ||
| Trace metals in a silicone foam cavity wound dressing | 147 | ||
| Applications of AAS in BP assays | 148 | ||
| Inductively coupled plasma emission spectroscopy | 148 | ||
| References | 149 | ||
| Further reading | 149 | ||
| 7 Molecular emission spectroscopy | 150 | ||
| Fluorescence spectrophotometry | 150 | ||
| Introduction | 151 | ||
| Instrumentation | 151 | ||
| Molecules which exhibit fluorescence | 152 | ||
| Factors interfering with fluorescence intensity | 154 | ||
| Applications of fluorescence spectrophotometry in pharmaceutical analysis | 154 | ||
| Determination of ethinylestradiol in tablets | 154 | ||
| Determination of the dissolution rate of digoxin tablets | 155 | ||
| Determination of aluminium in water for injection as a fluorescent complex | 155 | ||
| Determination of stability of peptide drugs in solution | 156 | ||
| Fluorescent derivatives and flow injection analysis | 156 | ||
| Raman spectroscopy | 157 | ||
| Introduction | 157 | ||
| Instrumentation | 158 | ||
| Applications | 159 | ||
| Rapid fingerprinting of drugs | 159 | ||
| Analysis of drugs in their formulations | 159 | ||
| A quantitative application | 159 | ||
| Control of the polymorphic forms of drugs in tablets | 160 | ||
| The development of spatially offset Raman spectroscopy (SORS) as a process control tool | 160 | ||
| Further reading | 162 | ||
| 8 Nuclear magnetic resonance spectroscopy | 163 | ||
| Introduction | 164 | ||
| Instrumentation | 165 | ||
| Proton (1H) NMR | 166 | ||
| Chemical shifts | 166 | ||
| Integration and equivalence | 171 | ||
| Multiplicity and spin–spin coupling | 174 | ||
| Splitting diagrams and spin systems | 178 | ||
| Application of NMR to structure confirmation in some drug molecules | 185 | ||
| Proton NMR spectrum of paracetamol | 185 | ||
| Proton NMR spectrum of aspirin | 185 | ||
| Proton NMR spectrum of salbutamol: a more complex example | 186 | ||
| Carbon NMR | 189 | ||
| Chemical shifts | 189 | ||
| An example of a 13C spectrum | 190 | ||
| Two-dimensional NMR spectra | 191 | ||
| Simple examples | 191 | ||
| A more complex example | 192 | ||
| Application of NMR to quantitative analysis | 195 | ||
| Other specialised applications of NMR | 197 | ||
| NMR in drug metabolism and related areas | 199 | ||
| Further reading | 199 | ||
| 9 Mass spectrometry | 200 | ||
| Introduction | 201 | ||
| Ion generation | 201 | ||
| Electrospray ionisation (ESI) (see Animation 9.1) | 201 | ||
| Atmospheric pressure chemical ionisation (APCI) | 205 | ||
| Electron impact ionisation (EI) (see Animation 9.4) | 205 | ||
| Matrix assisted laser desorption ionisation (MALDI) | 208 | ||
| Other ionisation methods | 210 | ||
| Ion separation techniques | 210 | ||
| Magnetic sector mass spectrometry | 210 | ||
| Magnetic sector instruments | 210 | ||
| Quadrupole instruments (see Animation 9.5) | 211 | ||
| Time of flight (TOF) ion separation (see Animation 9.6) | 212 | ||
| Ion trap separation (see Animation 9.8) | 213 | ||
| Fourier transform mass spectrometry | 214 | ||
| Calibration of the mass axes of mass spectrometers | 214 | ||
| A more detailed consideration of mass spectra | 216 | ||
| Mass spectra obtained under electron impact (EI) ionisation conditions | 216 | ||
| Molecular fragmentation patterns | 216 | ||
| Homolytic α-cleavage (see Animation 9.9) | 216 | ||
| Heterolytic cleavage (see Animation 9.10) | 217 | ||
| Fragmentation of aliphatic rings involving hydrogen transfer (see Animation 9.11) | 220 | ||
| Retro Diels–Alder fragmentation (see Animation 9.12) | 220 | ||
| McLafferty rearrangement (see Animation 9.13) | 221 | ||
| EI mass spectra where the molecular ion is abundant | 224 | ||
| Gas chromatography–mass spectrometry (GC–MS) | 227 | ||
| Applications of GC–MS with EI | 228 | ||
| Analysis of an essential oil | 228 | ||
| GC–MS of process intermediates and degradation products | 230 | ||
| Tandem mass spectrometry (see Animation 9.16) | 232 | ||
| High-resolution mass spectrometry | 240 | ||
| Mass spectrometry of proteins | 242 | ||
| Mass spectrometry in drug discovery | 244 | ||
| Reference | 246 | ||
| Further reading | 246 | ||
| 10 Chromatographic theory | 248 | ||
| Introduction | 248 | ||
| Void volume and capacity factor | 248 | ||
| Calculation of column efficiency | 249 | ||
| Origins of band broadening in HPLC | 251 | ||
| Van Deemter equation in liquid chromatography | 251 | ||
| Van Deemter equation in gas chromatography | 253 | ||
| Parameters used in evaluating column performance | 254 | ||
| Resolution | 255 | ||
| Peak asymmetry | 258 | ||
| Data acquisition | 258 | ||
| Report generation | 260 | ||
| Reference | 260 | ||
| 11 Gas chromatography | 261 | ||
| Introduction (see Animation 11.1) | 262 | ||
| Instrumentation | 262 | ||
| Syringes | 263 | ||
| Injection systems | 264 | ||
| Packed column injections | 264 | ||
| Split/splitless injection | 264 | ||
| Cool on-column injection | 266 | ||
| Programmable temperature vapouriser (see Animation 11.4) | 266 | ||
| GC oven | 267 | ||
| Types of columns | 267 | ||
| Packed columns | 267 | ||
| Capillary columns | 268 | ||
| Selectivity of liquid stationary phases | 268 | ||
| Kovats indices and column polarity | 268 | ||
| Examples of the separation of mixtures by GC | 269 | ||
| Analysis of peppermint oil on two GC phases | 269 | ||
| Analysis of the fatty acid composition of a fixed oil by GC | 272 | ||
| Chiral selectivity | 273 | ||
| Use of derivatisation in GC | 275 | ||
| Summary of parameters governing capillary GC performance | 279 | ||
| Carrier gas type/flow | 279 | ||
| Column temperature | 279 | ||
| Column length | 279 | ||
| Film thickness phase loading | 279 | ||
| Internal diameter | 279 | ||
| GC detectors (see Animation 11.5) | 280 | ||
| Applications of GC in quantitative analysis | 280 | ||
| Analysis of methyltestosterone in tablets | 282 | ||
| Data from analysis of methyltestosterone tablets | 283 | ||
| Analysis of atropine in eyedrops | 284 | ||
| Brief description of the assay | 285 | ||
| Data from analysis of eyedrop formulation | 285 | ||
| Quantification of ethanol in a formulation | 286 | ||
| Determination of manufacturing and degradation residues by GC | 287 | ||
| Determination of pivalic acid in dipivefrin eyedrops | 287 | ||
| Determination of dimethylaniline in bupivacaine injection (Fig. 11.25) | 287 | ||
| Determination of N,N-dimethylaniline in penicillins | 287 | ||
| Determination of a residual glutaraldehyde in a polymeric film | 289 | ||
| Determination of residual solvents | 289 | ||
| Typical BP procedures | 289 | ||
| Determination of residual solvents and volatile impurities by headspace analysis (see Animation 11.6) | 290 | ||
| Purge trap analysis | 292 | ||
| Solid-phase microextraction (SPME) (see Animation 11.7) | 292 | ||
| Applications of GC in bioanalysis | 293 | ||
| References | 295 | ||
| Further reading | 295 | ||
| 12 High-performance liquid chromatography | 296 | ||
| Introduction | 297 | ||
| Instrumentation (see Animation 12.2 and Animation 12.3) | 297 | ||
| Stationary and mobile phases | 298 | ||
| Structural factors which govern rate of elution of compounds from HPLC columns | 300 | ||
| Elution of neutral compounds | 300 | ||
| Control of elution rate of ionisable compounds by adjustment of pH of mobile phase | 303 | ||
| More advanced consideration of solvent selectivity in reverse-phase chromatography | 307 | ||
| Effect of temperature on HPLC | 310 | ||
| Summary of stationary phases used in HPLC | 311 | ||
| A more advanced consideration of reverse-phase stationary phases | 312 | ||
| (i) Retention factor for the lipophilic compound pentylbenzene, kPB | 313 | ||
| (ii) Hydrophobic selectivity αCH2 = kPB/kBB | 314 | ||
| (iii) Shape selectivity αT/O = kT/kO | 314 | ||
| (iv) Hydrogen bonding capacity αC/P = kC/kP | 314 | ||
| (v) Total ion exchange capacity aB/P = kB/kP (pH 7.6) | 315 | ||
| (vi) The acidic ion exchange capacity aB/P = kB/kP (pH 2.7) | 315 | ||
| Summary of detectors used in HPLC | 316 | ||
| Performance of a diode array detector | 317 | ||
| Applications of HPLC to the quantitative analysis of drugs in formulations | 321 | ||
| Analyses based on calibration with an external standard | 321 | ||
| Analysis of paracetamol tablets using a calibration curve | 322 | ||
| Tablets | 322 | ||
| Explanation of the assay | 322 | ||
| Assay | 322 | ||
| Data obtained | 323 | ||
| Assay of paracetamol and aspirin in tablets using a narrow-range calibration curve | 323 | ||
| Tablets | 323 | ||
| Explanation of the assay | 323 | ||
| Brief outline of the assay | 325 | ||
| Data obtained | 326 | ||
| Dilution of sample | 326 | ||
| Assay of active ingredients in an anaesthetic gel using a single-point calibration curve | 327 | ||
| Content per 100 g of gel | 327 | ||
| Explanation of the assay | 327 | ||
| Brief outline of the assay | 327 | ||
| Assays using calibration against an internal standard | 329 | ||
| Assay of hydrocortisone cream with one-point calibration against an internal standard | 330 | ||
| Explanation of the assay | 330 | ||
| Brief outline of the assay | 331 | ||
| Data obtained | 332 | ||
| Assay of miconazole cream with calibration against an internal standard over a narrow concentration range | 333 | ||
| Explanation of the assay | 333 | ||
| Brief outline of the assay | 333 | ||
| Data obtained | 334 | ||
| Assays involving more specialised HPLC techniques | 334 | ||
| Assay of adrenaline injection by chromatography with an anionic ion-pairing agent | 335 | ||
| Explanation of the assay | 335 | ||
| Assay of ascorbic acid by chromatography with a cationic ion-pairing agent and electrochemical detection | 335 | ||
| Assay of ascorbic acid by hydrophilic interaction chromatography | 336 | ||
| Assay of hyaluronic acid by size-exclusion chromatography (see Animation 12.10) | 337 | ||
| Methods used for the assay of proteins by HPLC | 339 | ||
| Analysis of non-ionic surfactants with an evaporative light scattering detector and gradient elution | 341 | ||
| Derivatisation in HPLC analysis | 342 | ||
| Separation of enantiomers by chiral HPLC | 343 | ||
| Ion chromatography | 345 | ||
| Ultra-high-performance liquid chromatography | 347 | ||
| References | 350 | ||
| Further reading | 350 | ||
| 13 Thin-layer chromatography | 351 | ||
| Introduction | 352 | ||
| Instrumentation | 352 | ||
| TLC chromatogram | 353 | ||
| Stationary phases | 354 | ||
| Elutropic series and mobile phases | 354 | ||
| Modification of TLC adsorbant | 357 | ||
| Treatment of silica gel with KOH | 357 | ||
| Silanised silica gel | 358 | ||
| Keiselguhr as an inert support | 358 | ||
| Detection of compounds on TLC plates following development | 359 | ||
| Ultraviolet light | 359 | ||
| Location reagents | 359 | ||
| Iodine vapour | 359 | ||
| Potassium permanganate | 360 | ||
| Ninhydrin solution | 360 | ||
| Alkaline tetrazolium blue | 360 | ||
| Ethanol/sulphuric acid 20% | 360 | ||
| Applications of TLC analysis | 360 | ||
| Qualitative identity tests | 360 | ||
| Limit tests | 360 | ||
| Where the structure of the impurity is known | 360 | ||
| Where the structure of the impurity is unknown | 363 | ||
| Tests in which known and unknown standards are used | 364 | ||
| High-performance TLC (HPTLC) | 365 | ||
| Applications of HPTLC | 365 | ||
| References | 367 | ||
| Further reading | 367 | ||
| 14 High-performance capillary electrophoresis | 368 | ||
| Introduction | 369 | ||
| Electrophoresis | 369 | ||
| Electro-osmotic flow (EOF) (see Animation 14.1) | 370 | ||
| Migration in Capillary electrophoresis (CE) (see Animation 14.2) | 371 | ||
| Instrumentation | 372 | ||
| Control of separation | 372 | ||
| Migration time | 372 | ||
| Dispersion | 374 | ||
| Longitudinal diffusion | 374 | ||
| Injection plug length | 374 | ||
| Joule heating | 374 | ||
| Solute/wall interactions | 374 | ||
| Electrodispersion | 375 | ||
| Applications of CE in pharmaceutical analysis | 375 | ||
| Separation of atenolol and related impurities predominantly on the basis of charge | 375 | ||
| Separation predominantly on the basis of ionic radius | 376 | ||
| Analysis of non-steroidal anti-inflammatory drugs (NSAIDs) by CE and separation of anions on the basis of ionic radius | 378 | ||
| Separation of peptides | 378 | ||
| Use of additives in the running buffer | 379 | ||
| Applications of cyclodextrins in producing improvements in separation | 380 | ||
| Separation of pilocarpine from its epimer | 380 | ||
| Separation of chiral local anaesthetics | 380 | ||
| Micellar electrokinetic chromatography (MEKC) | 382 | ||
| Separation of cefotaxime from related impurities | 382 | ||
| Analysis of flavonoids by MEKC | 383 | ||
| Capillary electrophoresis with indirect detection | 384 | ||
| Affinity capillary electrophoresis | 386 | ||
| Capillary electro-chromatography (CEC) | 386 | ||
| References | 387 | ||
| Further reading | 388 | ||
| 15 Extraction methods in pharmaceutical analysis | 389 | ||
| Introduction | 390 | ||
| Commonly used excipients in formulations | 390 | ||
| Tablets and capsules | 390 | ||
| Suspensions and solutions | 391 | ||
| Creams and ointments | 391 | ||
| Solvent extraction methods | 391 | ||
| Extraction of organic bases and acids utilising their ionised and un-ionised forms | 391 | ||
| Partitioning between organic solvents | 392 | ||
| Ion pair extraction | 393 | ||
| Derivatisation prior to extraction | 393 | ||
| Supercritical fluid extraction | 394 | ||
| Microdialysis extraction | 395 | ||
| Solid-phase extraction (SPE) | 395 | ||
| Introduction | 396 | ||
| Methodology | 396 | ||
| Types of adsorbants used in SPE | 398 | ||
| Lipophilic silica gels | 398 | ||
| Typical extraction methodologies using lipophilic silica gels | 399 | ||
| Polar surface-modified silica gels | 399 | ||
| Typical methodologies using straight-phase adsorbants | 399 | ||
| Anion exchangers based on surface-modified silica gels | 400 | ||
| Cation exchangers based on surface-modified silica gels | 401 | ||
| Factors requiring attention in SPE with silica gels | 402 | ||
| Borate gels (Fig. 15.12) | 402 | ||
| Immunoaffinity gels | 403 | ||
| Adaptation of SPE for automated on-line extraction prior to HPLC analysis | 403 | ||
| Recent developments in solid-phase and on-line extraction | 404 | ||
| References | 405 | ||
| Further reading | 405 | ||
| 16 Methods used in the quality control of biotechnologically produced drugs | 406 | ||
| Protein drugs | 407 | ||
| Protein structure | 408 | ||
| Amino acids and amino acid sequences | 408 | ||
| Polar amino acids | 409 | ||
| Hydrophobic amino acids | 409 | ||
| Charged amino acids | 410 | ||
| The peptide bond and the primary structure of proteins | 411 | ||
| Protein secondary structure | 414 | ||
| Protein tertiary structure | 416 | ||
| Instrumental techniques used in the analysis of biotechnologically produced drugs | 417 | ||
| Introduction | 417 | ||
| Size exclusion chromatography (SEC) | 418 | ||
| Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDSPAGE) | 420 | ||
| Isoelectric focusing | 422 | ||
| Alteplase glycoforms | 424 | ||
| Molgramostim identification test | 424 | ||
| Other pharmacopoeial tests using isoelectric focusing | 424 | ||
| Binding assays used in pharmacopoeial tests on protein drugs | 425 | ||
| Enzyme-linked immunosorbant assay (ELISA) | 425 | ||
| Applications of ELISA in the pharmacopoeias | 425 | ||
| Radio-immunoassay (RIA) | 425 | ||
| Polymerase chain reaction (PCR) | 426 | ||
| Capillary electrophoresis | 427 | ||
| Fingerprinting by HPLC and HPLC-MS | 428 | ||
| The Edman reaction | 430 | ||
| Methods used to assess the secondary and tertiary structure of protein drugs | 430 | ||
| Circular dichroism | 431 | ||
| Other techniques used to assess protein secondary structure | 433 | ||
| Reference | 434 | ||
| Further reading | 434 | ||
| 17 Electrochemical biosensors | 435 | ||
| Introduction | 435 | ||
| Basic principles of electrochemistry | 436 | ||
| Types of electrochemical biosensors | 438 | ||
| First-generation biosensors | 439 | ||
| Second-generation biosensors | 440 | ||
| Third-generation biosensors | 440 | ||
| Instrumentation | 441 | ||
| Examples of biosensors utilised for pharmaceutical analysis | 442 | ||
| Detection of blood glucose levels | 442 | ||
| Detection of cholesterol | 445 | ||
| Detection of pharmaceutical drugs | 445 | ||
| Limitations of biosensors in pharmaceutical analysis | 446 | ||
| References | 447 | ||
| Further reading | 447 | ||
| Answers to Self-tests | e1 | ||
| Chapter 1 | e1 | ||
| Self-test 1.1 | e1 | ||
| Self-test 1.2 | e1 | ||
| Self-test 1.3 | e1 | ||
| Self-test 1.4 | e1 | ||
| Self-test 1.5 | e1 | ||
| Self-test 1.6 | e1 | ||
| Self-test 1.7 | e1 | ||
| Self-test 1.8 | e2 | ||
| Self-test 1.9 | e2 | ||
| Self-test 1.10 | e2 | ||
| Self-test 1.11 | e2 | ||
| Chapter 2 | e2 | ||
| Self-test 2.1 | e2 | ||
| Self-test 2.2 | e2 | ||
| Self-test 2.3 | e2 | ||
| Self-test 2.4 | e2 | ||
| Self-test 2.5 | e2 | ||
| Self-test 2.6 | e2 | ||
| Self-test 2.7 | e2 | ||
| Self-test 2.8 | e3 | ||
| Self-test 2.9 | e3 | ||
| Self-test 2.10 | e3 | ||
| Self-test 2.11 | e3 | ||
| Self-test 2.12 | e3 | ||
| Self-test 2.13 | e3 | ||
| Self-test 2.14 | e3 | ||
| Self-test 2.15 | e3 | ||
| Self-test 2.16 | e3 | ||
| Self-test 2.17 | e3 | ||
| Chapter 3 | e3 | ||
| Self-test 3.1 | e3 | ||
| Self-test 3.2 | e3 | ||
| Self-test 3.3 | e3 | ||
| Self-test 3.4 | e3 | ||
| Self-test 3.5 | e4 | ||
| Self-test 3.6 | e4 | ||
| Self-test 3.7 | e4 | ||
| Self-test 3.8 | e4 | ||
| Self-test 3.9 | e4 | ||
| Self-test 3.10 | e4 | ||
| Chapter 4 | e4 | ||
| Self-test 4.1 | e4 | ||
| Self-test 4.2 | e4 | ||
| Self-test 4.3 | e4 | ||
| Self-test 4.4 | e4 | ||
| Self-test 4.5 | e4 | ||
| Self-test 4.6 | e4 | ||
| Self-test 4.7 | e4 | ||
| Chapter 5 | e5 | ||
| Self-test 5.1 | e5 | ||
| Self-test 5.2 | e5 | ||
| Self-test 5.3 | e5 | ||
| Self-test 5.4 | e5 | ||
| Chapter 6 | e5 | ||
| Self-test 6.1 | e5 | ||
| Self-test 6.2 | e5 | ||
| Self-test 6.3 | e5 | ||
| Self-test 6.4 | e5 | ||
| Self-test 6.5 | e5 | ||
| Self-test 6.6 | e5 | ||
| Chapter 8 | e5 | ||
| Self-test 8.1 | e5 | ||
| Self-test 8.2 | e5 | ||
| Self-test 8.3 | e6 | ||
| Self-test 8.4 | e6 | ||
| Self-test 8.5 | e6 | ||
| Self-test 8.6 | e6 | ||
| Self-test 8.7 | e6 | ||
| Self-test 8.8 | e6 | ||
| Self-test 8.9 | e6 | ||
| Self-test 8.10 | e6 | ||
| Chapter 9 | e6 | ||
| Self-test 9.1 | e6 | ||
| Self-test 9.2 | e7 | ||
| Self-test 9.3 | e7 | ||
| Self-test 9.4 | e7 | ||
| Self-test 9.5 | e7 | ||
| Self-test 9.6 | e8 | ||
| Self-test 9.7 | e8 | ||
| Self-test 9.8 | e8 | ||
| Self-test 9.9 | e8 | ||
| Self-test 9.10 | e8 | ||
| Self-test 9.11 | e9 | ||
| Self-test 9.12 | e9 | ||
| Self-test 9.13 | e9 | ||
| Chapter 10 | e9 | ||
| Self-test 10.1 | e9 | ||
| Self-test 10.2 | e9 | ||
| Self-test 10.3 | e9 | ||
| Self-test 10.4 | e10 | ||
| Chapter 11 | e10 | ||
| Self-test 11.1 | e10 | ||
| Self-test 11.2 | e10 | ||
| Self-test 11.3 | e10 | ||
| Self-test 11.4 | e10 | ||
| Self-test 11.5 | e10 | ||
| Self-test 11.6 | e10 | ||
| Self-test 11.7 | e10 | ||
| Chapter 12 | e10 | ||
| Self-test 12.1 | e10 | ||
| Self-test 12.2 | e10 | ||
| Self-test 12.3 | e10 | ||
| Self-test 12.5 | e11 | ||
| Self-test 12.6 | e11 | ||
| Self-test 12.7 | e11 | ||
| Self-test 12.8 | e11 | ||
| Self-test 12.9 | e11 | ||
| Self-test 12.10 | e11 | ||
| Self-test 12.11 | e11 | ||
| Chapter 13 | e11 | ||
| Self-test 13.1 | e11 | ||
| Self-test 13.2 | e11 | ||
| Self-test 13.3 | e11 | ||
| Self-test 13.4 | e11 | ||
| Self-test 13.5 | e11 | ||
| Chapter 14 | e12 | ||
| Self-test 14.1 | e12 | ||
| Chapter 16 | e12 | ||
| Self-test 16.1 | e12 | ||
| Self-test 16.2 | e12 | ||
| Self-test 16.3 | e12 | ||
| Self-test 16.4 | e12 | ||
| Self-test 16.5 | e12 | ||
| Self-test 16.6 | e12 | ||
| Self-test 16.7 | e13 | ||
| Chapter 17 | e13 | ||
| Self-test 17.1 | e13 | ||
| Self-test 17.2 | e13 | ||
| Index | 448 | ||
| A | 448 | ||
| B | 449 | ||
| C | 450 | ||
| D | 451 | ||
| E | 452 | ||
| F | 452 | ||
| G | 453 | ||
| H | 453 | ||
| I | 454 | ||
| J | 455 | ||
| K | 455 | ||
| L | 455 | ||
| M | 455 | ||
| N | 456 | ||
| O | 457 | ||
| P | 457 | ||
| Q | 458 | ||
| R | 458 | ||
| S | 459 | ||
| T | 460 | ||
| U | 460 | ||
| V | 461 | ||
| W | 461 | ||
| X | 461 | ||
| Z | 461 |