Additional Information
Book Details
Abstract
An introductory text, written with the needs of the student in mind, which explains all the most important techniques used in the analysis of pharmaceuticals - a key procedure in ensuring the quality of drugs . The text is enhanced throughout with keypoints and self-assessment boxes, to aid student learning.
Features
- Includes worked calculations to demonstrate mathematics in use for pharmaceutical analysis.
- Focuses on key points rather than a large number of facts to help readers really understand the field as well as pass exams.
- Includes self-assessment, focussing on simple arithmetical calculation results from analytical data.
- Additional section on basic calculations in pharmaceutical analysis
- More detail on the capillary electrophoresis of proteins
- A discussion of some of the new types of HPLC column and on solvent selectivity in HPLC
- Additional material inserted on the control of the quality of analytical methods, mass spectrometry and high pressure liquid chromatography
- Additional self-assessment exercises
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Pharmaceutical Analysis: A Textbook for Pharmacy Students and Pharmaceutical Chemists | iii | ||
| Copyright\r | iv | ||
| Preface to the third edition\r | v | ||
| Contents | vii | ||
| Chapter 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 | ||
| 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 | 10 | ||
| 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 | 16 | ||
| Linearity | 16 | ||
| 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 | ||
| Chapter 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 | 28 | ||
| Acidic and basic strength and pKa | 29 | ||
| Henderson-Hasselbalch equation | 29 | ||
| Ionisation of drug molecules | 31 | ||
| Diphenhydramine | 32 | ||
| Ibuprofen | 32 | ||
| Buffers | 33 | ||
| Salt hydrolysis | 36 | ||
| Activity, ionic strength and dielectric constant | 37 | ||
| Partition coefficient | 38 | ||
| Effect of pH on partitioning | 40 | ||
| Drug stability | 41 | ||
| Zero-order degradation | 42 | ||
| First-order degradation | 42 | ||
| Stereochemistry of drugs | 43 | ||
| Geometrical isomerism | 43 | ||
| Chirality and optical isomerism | 44 | ||
| Diastereoisomers | 47 | ||
| Measurement of optical rotation | 49 | ||
| Profiles of physico-chemical properties of some drug molecules | 50 | ||
| Procaine | 50 | ||
| Paracetamol | 51 | ||
| Aspirin | 52 | ||
| Benzylpenicillin | 52 | ||
| 5-Fluorouracil | 53 | ||
| Acebutolol | 54 | ||
| Sulfadiazine | 54 | ||
| Isoprenaline | 55 | ||
| Prednisolone | 55 | ||
| Guanethidine | 56 | ||
| Pyridostigmine bromide | 56 | ||
| References | 59 | ||
| Useful weblinks | 59 | ||
| Chapter 3: Titrimetric and chemical analysis methods | 60 | ||
| Introduction | 61 | ||
| Instrumentation and reagents | 61 | ||
| Glassware | 61 | ||
| Primary standards and standard solutions | 61 | ||
| Direct acid/base titrations in the aqueous phase | 62 | ||
| Strong acid/strong base titrations | 62 | ||
| Weak acid/strong base and weak base/strong acid titrations | 63 | ||
| Titrations of the salts of weak bases in mixed aqueous/non-aqueous media | 65 | ||
| Indirect titrations in the aqueous phase | 66 | ||
| Estimation of esters by back titration | 66 | ||
| Saponification value | 66 | ||
| Estimation of alcohols and hydroxyl values by reaction with acetic anhydride (AA) | 67 | ||
| Non-aqueous titrations | 68 | ||
| Theory | 68 | ||
| Non-aqueous titration of weak bases | 69 | ||
| Non-aqueous titration of weak acids | 70 | ||
| Argentimetric titrations | 70 | ||
| Compleximetric titrations | 70 | ||
| Redox titrations | 71 | ||
| Theory | 71 | ||
| Iodometric titrations | 73 | ||
| Direct titrations | 73 | ||
| Iodine displacement titrations | 74 | ||
| Iodine-absorbing substances in penicillins | 75 | ||
| Ion pair titrations | 75 | ||
| Titrations using indicator dyes | 76 | ||
| Titrations using iodide as a lipophilic anion | 76 | ||
| Diazotisation titrations | 76 | ||
| Potentiometric titrations | 77 | ||
| Potentiometric end-point detection | 77 | ||
| Use of potentiometric titration to determine pKa values | 80 | ||
| Karl Fischer titration (coulometric end-point detection) | 81 | ||
| Automation of wet chemical methods | 82 | ||
| Automatic titration (Fig. 3.21) | 82 | ||
| Flow injection analysis | 83 | ||
| Applications of FIA in pharmaceutical analysis | 84 | ||
| Determination of chloroxine | 84 | ||
| Determination of captopril | 85 | ||
| Determination of non-steroidal anti-inflammatory drugs | 85 | ||
| Determination of promethazine | 85 | ||
| Determination of chlorocresol | 85 | ||
| Limit test for heavy metals | 85 | ||
| Use of segmented flow in determination of partition coefficients | 86 | ||
| Automated dissolution testing | 86 | ||
| References | 89 | ||
| Further reading | 89 | ||
| Useful websites | 89 | ||
| Chapter 4: Ultraviolet and visible spectroscopy | 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 | ||
| Calibration of absorbance scale | 97 | ||
| Calibration of wavelength scale | 97 | ||
| Determination of instrumental resolution | 97 | ||
| Determination of stray light | 98 | ||
| UV spectra of some representative drug molecules | 98 | ||
| Steroid enones | 98 | ||
| Ephedrine: the benzoid chromophore | 99 | ||
| Ketoprofen: extended benzene chromophore | 99 | ||
| Procaine: amino group auxochrome | 100 | ||
| Phenylephrine: hydroxyl group auxochrome | 100 | ||
| Use of UV/visible spectrophotometry to determine pKa values | 102 | ||
| Applications of UV/visible spectroscopy to pharmaceutical quantitative analysis | 103 | ||
| Assay examples | 103 | ||
| Furosemide (frusemide) in tablet form | 103 | ||
| Assay of cyclizine lactate in an injection | 103 | ||
| Assay of penicillins by derivatisation (Fig. 4.12) | 105 | ||
| Assay of adrenaline in lidocaine (lignocaine) adrenaline injection | 106 | ||
| Difference spectrophotometry | 107 | ||
| Analysis of aspirin in dextropropoxyphene compound tablets | 107 | ||
| Derivative spectra | 109 | ||
| Applications of UV/visible spectroscopy in preformulation and formulation | 112 | ||
| Partition coefficient | 112 | ||
| Solubility | 112 | ||
| Release of a drug from a formulation | 112 | ||
| References | 114 | ||
| Further reading | 114 | ||
| Useful websites | 114 | ||
| Chapter 5: Infrared spectrophotometry | 115 | ||
| Introduction | 116 | ||
| Factors determining intensity and energy level of absorption in IR spectra | 117 | ||
| Intensity of absorption | 117 | ||
| Energy level of absorption | 118 | ||
| Instrumentation | 118 | ||
| Instrument calibration | 120 | ||
| 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 | ||
| Preparation of samples for fingerprint determination | 127 | ||
| Infrared spectrophotometry as a method for identifying polymorphs | 130 | ||
| Near-infrared analysis (NIRA) | 130 | ||
| Introduction | 131 | ||
| Examples of NIRA applications | 131 | ||
| Determination of particle size in United States Pharmacopoeia (USP) grade aspirin | 132 | ||
| Determination of blend uniformity | 132 | ||
| Determination of active ingredients in multicomponent dosage forms | 133 | ||
| In-pack determination of active ingredients | 133 | ||
| Determination of polymorphs | 133 | ||
| Moisture determination | 134 | ||
| Process control of components in a shampoo | 134 | ||
| References | 136 | ||
| Further reading | 136 | ||
| Additional reading | 137 | ||
| Useful websites | 137 | ||
| Chapter 6: Atomic spectrophotometry | 138 | ||
| Atomic emission spectrophotometry (AES) | 138 | ||
| Introduction | 138 | ||
| Instrumentation | 139 | ||
| Examples of quantitation by AES | 140 | ||
| Assay of sodium and potassium ions in an i.v. infusion | 140 | ||
| Interferences in AES analysis | 142 | ||
| Ionisation | 142 | ||
| Viscosity | 142 | ||
| Anionic interference | 142 | ||
| Assays based on the method of standard additions | 143 | ||
| Assay for KCl, NaCl and glucose i.v. infusion | 143 | ||
| Atomic absorption spectrophotometry (AAS) | 145 | ||
| Introduction | 145 | ||
| Instrumentation | 146 | ||
| Examples of assays using AAS | 146 | ||
| Assay of calcium and magnesium in haemodialysis fluid | 147 | ||
| Some examples of limit tests employing AAS | 148 | ||
| Assay of lead in sugars | 148 | ||
| Trace metals in a silicone foam cavity wound dressing | 150 | ||
| Applications of AAS in BP assays | 150 | ||
| Inductively coupled plasma emission spectroscopy | 150 | ||
| References | 151 | ||
| Further reading | 151 | ||
| Useful websites | 151 | ||
| Chapter 7: Molecular emission spectroscopy | 152 | ||
| Fluorescence spectrophotometry | 152 | ||
| Introduction | 153 | ||
| Instrumentation | 154 | ||
| Molecules which exhibit fluorescence | 154 | ||
| Factors interfering with fluorescence intensity | 155 | ||
| Applications of fluorescence spectrophotometry in pharmaceutical analysis | 156 | ||
| Determination of ethinylestradiol in tablets | 156 | ||
| Determination of the dissolution rate of digoxin tablets | 157 | ||
| Determination of aluminium in water for injection as a fluorescent complex | 158 | ||
| Determination of stability of peptide drugs in solution | 158 | ||
| Fluorescent derivatives and flow injection analysis | 158 | ||
| Raman spectroscopy | 159 | ||
| Introduction | 160 | ||
| Instrumentation | 161 | ||
| Applications | 161 | ||
| Rapid fingerprinting of drugs | 161 | ||
| Analysis of drugs in their formulations | 162 | ||
| A quantitative application | 162 | ||
| Control of the polymorphic forms of drugs in tablets | 163 | ||
| References | 164 | ||
| Further reading | 164 | ||
| Useful websites | 164 | ||
| Chapter 8: Nuclear magnetic resonance spectroscopy | 165 | ||
| Introduction | 166 | ||
| Instrumentation | 167 | ||
| Proton (1H) NMR | 168 | ||
| Chemical shifts | 168 | ||
| Integration and equivalence | 173 | ||
| Multiplicity and spin-spin coupling | 175 | ||
| Splitting diagrams and spin systems | 181 | ||
| Application of NMR to structure confirmation in some drug molecules | 188 | ||
| Proton NMR spectrum of paracetamol | 188 | ||
| Proton NMR spectrum of aspirin | 188 | ||
| Proton NMR spectrum of salbutamol: a more complex example | 189 | ||
| Carbon NMR | 192 | ||
| Chemical shifts | 192 | ||
| An example of a 13C spectrum | 193 | ||
| Two-dimensional NMR spectra | 194 | ||
| Simple examples | 194 | ||
| A more complex example | 196 | ||
| Application of NMR to quantitative analysis | 199 | ||
| Other specialised applications of NMR | 200 | ||
| NMR in drug metabolism and related areas | 202 | ||
| Further reading | 203 | ||
| Useful websites | 203 | ||
| Chapter 9: Mass spectrometry | 204 | ||
| Introduction | 205 | ||
| Ion generation | 205 | ||
| Electrospray ionisation (ESI) | 205 | ||
| Atmospheric pressure chemical ionisation (APCI) | 209 | ||
| Electron impact ionisation (EI) | 209 | ||
| Matrix assisted laser desorption ionisation (MALDI) | 213 | ||
| Other ionisation methods | 214 | ||
| Ion separation techniques | 215 | ||
| Magnetic sector mass spectrometry | 215 | ||
| Magnetic sector instruments | 215 | ||
| Quadrupole instruments | 216 | ||
| Time of flight (TOF) ion separation | 216 | ||
| Ion trap separation | 217 | ||
| Fourier transform mass spectrometry | 218 | ||
| Calibration of the mass axes of mass spectrometers | 218 | ||
| A more detailed consideration of mass spectra | 219 | ||
| Mass spectra obtained under electron impact (EI) ionisation conditions | 219 | ||
| Molecular fragmentation patterns | 220 | ||
| Homolytic α-cleavage | 220 | ||
| Heterolytic cleavage | 221 | ||
| Fragmentation of aliphatic rings involving hydrogen transfer | 222 | ||
| Retro Diels-Alder fragmentation | 223 | ||
| McLafferty rearrangement | 226 | ||
| EI mass spectra where the molecular ion is abundant | 228 | ||
| Gas chromatography-mass spectrometry (GC-MS) | 231 | ||
| Applications of GC-MS with EI | 232 | ||
| Analysis of an essential oil | 232 | ||
| GC-MS of process intermediates and degradation products | 234 | ||
| Tandem mass spectrometry | 236 | ||
| High-resolution mass spectrometry | 244 | ||
| Mass spectrometry of proteins | 246 | ||
| Mass spectrometry in drug discovery | 248 | ||
| Reference | 251 | ||
| Further reading | 251 | ||
| Useful websites | 251 | ||
| Chapter 10: Chromatographic theory | 252 | ||
| Introduction | 252 | ||
| Void volume and capacity factor | 252 | ||
| Calculation of column efficiency | 253 | ||
| Origins of band broadening in HPLC | 254 | ||
| Van Deemter equation in liquid chromatography | 254 | ||
| Van Deemter equation in gas chromatography | 257 | ||
| Parameters used in evaluating column performance | 258 | ||
| Resolution | 259 | ||
| Peak asymmetry | 261 | ||
| Data acquisition | 262 | ||
| Report generation | 263 | ||
| Reference | 264 | ||
| Chapter 11: Gas chromatography | 265 | ||
| Introduction | 266 | ||
| Instrumentation | 266 | ||
| Syringes | 267 | ||
| Injection systems | 268 | ||
| Packed column injections | 268 | ||
| Split/splitless injection | 268 | ||
| Cool on-column injection | 270 | ||
| Programmable temperature vapouriser | 270 | ||
| GC oven | 271 | ||
| Types of column | 271 | ||
| Packed columns | 271 | ||
| Capillary columns | 272 | ||
| Selectivity of liquid stationary phases | 272 | ||
| Kovats indices and column polarity | 272 | ||
| Examples of the separation of mixtures by GC | 273 | ||
| Analysis of peppermint oil on two GC phases | 273 | ||
| Analysis of the fatty acid composition of a fixed oil by GC | 276 | ||
| Chiral selectivity | 277 | ||
| Use of derivatisation in GC | 280 | ||
| Summary of parameters governing capillary GC performance | 283 | ||
| Carrier gas type/flow | 283 | ||
| Column temperature | 283 | ||
| Column length | 283 | ||
| Film thickness phase loading | 284 | ||
| Internal diameter | 284 | ||
| GC detectors | 284 | ||
| Applications of GC in quantitative analysis | 284 | ||
| Analysis of methyltestosterone in tablets | 287 | ||
| Data from analysis of methyltestosterone tablets | 287 | ||
| Analysis of atropine in eyedrops | 288 | ||
| Brief description of the assay | 289 | ||
| Data from analysis of eyedrop formulation | 289 | ||
| Quantification of ethanol in a formulation | 290 | ||
| Determination of manufacturing and degradation residues by GC | 291 | ||
| Determination of pivalic acid in dipivefrin eye drops | 291 | ||
| Determination of dimethylaniline in bupivacaine injection (Fig. 11.25) | 291 | ||
| Determination of N,N-dimethylaniline in penicillins | 292 | ||
| Determination of a residual glutaraldehyde in a polymeric film | 293 | ||
| Determination of residual solvents | 294 | ||
| Typical BP procedures | 294 | ||
| Determination of residual solvents and volatile impurities by headspace analysis | 294 | ||
| Purge trap analysis | 297 | ||
| Solid-phase microextraction (SPME) | 297 | ||
| Applications of GC in bioanalysis | 298 | ||
| References | 300 | ||
| Further reading | 300 | ||
| Useful websites | 300 | ||
| Chapter 12: High-performance liquid chromatography | 301 | ||
| Introduction | 302 | ||
| Instrumentation | 302 | ||
| Stationary and mobile phases | 303 | ||
| Structural factors which govern rate of elution of compounds from HPLC columns | 306 | ||
| Elution of neutral compounds | 306 | ||
| Control of elution rate of ionisable compounds by adjustment of pH of mobile phase | 308 | ||
| 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 | ||
| (i). Retention factor for the lipophilic compound pentylbenzene, kPB | 320 | ||
| (ii). Hydrophobic selectivity αCH2 = kPB/kBB | 320 | ||
| (iii). Shape selectivity αT/O = kT/kO | 320 | ||
| (iv). Hydrogen bonding capacity αC/P = kC/kP | 321 | ||
| (v). Total ion exchange capacity aB/P = kB/kP (pH 7.6) | 321 | ||
| (vi). The acidic ion exchange capacity aB/P = kB/kP (pH 2.7) | 321 | ||
| 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 | ||
| Analyses based on calibration with an external standard | 327 | ||
| Analysis of paracetamol tablets using a calibration curve | 328 | ||
| Tablets | 328 | ||
| Explanation of the assay | 328 | ||
| Assay | 329 | ||
| Data obtained | 329 | ||
| Assay of paracetamol and aspirin in tablets using a narrow-range calibration curve | 331 | ||
| Tablets | 331 | ||
| Explanation of the assay | 331 | ||
| Brief outline of the assay | 332 | ||
| Data obtained | 332 | ||
| Dilution of sample | 332 | ||
| Assay of active ingredients in an anaesthetic gel using a single point calibration curve | 333 | ||
| Content per 100g of gel | 333 | ||
| Explanation of the assay | 333 | ||
| Brief outline of the assay | 333 | ||
| Assays using calibration against an internal standard | 335 | ||
| Assay of hydrocortisone cream with one-point calibration against an internal standard | 336 | ||
| Explanation of the assay | 336 | ||
| Brief outline of the assay | 337 | ||
| Data obtained | 338 | ||
| Assay of miconazole cream with calibration against an internal standard over a narrow concentration range | 339 | ||
| Explanation of the assay | 339 | ||
| Brief outline of the assay | 339 | ||
| Data obtained | 340 | ||
| Assays involving more specialised HPLC techniques | 340 | ||
| Assay of adrenaline injection by chromatography with an anionic ion-pairing agent | 341 | ||
| Explanation of the assay | 341 | ||
| Assay of ascorbic acid by chromatography with a cationic ion-pairing agent and electrochemical detection | 341 | ||
| Assay of ascorbic acid by hydrophilic interaction chromatography | 342 | ||
| Assay of hyaluronic acid by size-exclusion chromatography | 344 | ||
| Methods used for the assay of proteins by HPLC | 346 | ||
| Analysis of non-ionic surfactants with an evaporative light scattering detector and gradient elution | 347 | ||
| Derivatisation in HPLC analysis | 348 | ||
| Separation of enantiomers by chiral HPLC | 349 | ||
| Ion chromatography | 352 | ||
| Ultra-high-performance liquid chromatography | 353 | ||
| References | 356 | ||
| Further reading | 357 | ||
| Useful websites | 357 | ||
| Chapter 13: Thin-layer chromatography | 358 | ||
| Introduction | 359 | ||
| Instrumentation | 359 | ||
| TLC chromatogram | 360 | ||
| Stationary phases | 361 | ||
| Elutropic series and mobile phases | 361 | ||
| Modification of TLC adsorbant | 365 | ||
| Treatment of silica gel with KOH | 365 | ||
| Silanised silica gel | 365 | ||
| Keiselguhr as an inert support | 366 | ||
| Detection of compounds on TLC plates following development | 366 | ||
| Ultraviolet light | 366 | ||
| Location reagents | 366 | ||
| Iodine vapour | 367 | ||
| Potassium permanganate | 367 | ||
| Ninhydrin solution | 367 | ||
| Alkaline tetrazolium blue | 367 | ||
| Ethanol/sulphuric acid 20% | 367 | ||
| Applications of TLC analysis | 367 | ||
| Qualitative identity tests | 367 | ||
| Limit tests | 368 | ||
| Where the stucture of the impurity is known | 368 | ||
| Where the structure of the impurity is unknown | 370 | ||
| Tests in which known and unknown standards are used | 372 | ||
| High-performance TLC (HPTLC) | 372 | ||
| Applications of HPTLC | 373 | ||
| References | 374 | ||
| Further reading | 374 | ||
| Chapter 14: High-performance capillary electrophoresis | 376 | ||
| Introduction | 377 | ||
| Electrophoresis | 377 | ||
| EOF | 379 | ||
| Migration in CE | 379 | ||
| Instrumentation | 380 | ||
| Control of separation | 382 | ||
| Migration time | 382 | ||
| Dispersion | 382 | ||
| Longitudinal diffusion | 382 | ||
| Injection plug length | 383 | ||
| Joule heating | 383 | ||
| Solute/wall interactions | 383 | ||
| Electrodispersion | 383 | ||
| Applications of CE in pharmaceutical analysis | 384 | ||
| Separation of atenolol and related impurities predominantly on the basis of charge | 384 | ||
| Separation predominantly on the basis of ionic radius | 385 | ||
| Analysis of non-steroidal anti-inflammatory drugs (NSAIDs) by CE and separation of anions on the basis of ionic radius | 386 | ||
| Separation of peptides | 387 | ||
| Use of additives in the running buffer | 388 | ||
| Applications of cyclodextrins in producing improvements in separation | 388 | ||
| Separation of pilocarpine from its epimer | 389 | ||
| Separation of chiral local anaesthetics | 389 | ||
| Micellar electrokinetic chromatography (MEKC) | 391 | ||
| Separation of cefotaxime from related impurities | 391 | ||
| Analysis of flavonoids by MEKC | 393 | ||
| Capillary electrophoresis with indirect detection | 393 | ||
| Affinity capillary electrophoresis | 395 | ||
| Capillary electro-chromatography (CEC) | 396 | ||
| References | 397 | ||
| Further reading | 397 | ||
| Useful websites | 397 | ||
| Chapter 15: Extraction methods in pharmaceutical analysis | 398 | ||
| Introduction | 399 | ||
| Commonly used excipients in formulations | 399 | ||
| Tablets and capsules | 399 | ||
| Suspensions and solutions | 400 | ||
| Creams and ointments | 400 | ||
| Solvent extraction methods | 400 | ||
| Extraction of organic bases and acids utilising their ionised and un-ionised forms | 400 | ||
| Partitioning between organic solvents | 402 | ||
| Ion pair extraction | 402 | ||
| Derivatisation prior to extraction | 403 | ||
| Supercritical fluid extraction | 403 | ||
| Microdialysis extraction | 404 | ||
| Solid-phase extraction (SPE) | 404 | ||
| Introduction | 405 | ||
| Methodology | 405 | ||
| Types of adsorbants used in SPE | 407 | ||
| Lipophilic silica gels | 407 | ||
| Typical extraction methodologies using lipophilic silica gels | 408 | ||
| Polar surface-modified silica gels | 409 | ||
| Typical methodologies using straight-phase adsorbants | 409 | ||
| Anion exchangers based on surface-modified silica gels | 410 | ||
| Cation exchangers based on surface-modified silica gels | 410 | ||
| Factors requiring attention in SPE with silica gels | 411 | ||
| Borate gels (Fig. 15.12) | 412 | ||
| Immunoaffinity gels | 412 | ||
| Adaptation of SPE for automated on-line extraction prior to HPLC analysis | 413 | ||
| Recent developments in solid-phase and on-line extraction | 414 | ||
| References | 414 | ||
| Further reading | 414 | ||
| Index | 417 |