Essentials of Pharmaceutical Chemistry

Cover
Title page
Half title page
Dedication
Contents
Preface to the fourth edition
Acknowledgements
About the author
Chemistry of acids and bases
	Dissociation of weak acids and bases
	Hydrolysis of salts
	Amphiprotic salts
	Buffer solutions
	Buffer capacity
	Biological buffers
	Ionisation of drugs
	pKa values of drug molecules
	pH indicators
	Tutorial examples
	Problems
Partition coefficient and biopharmacy
	Experimental measurement of the partition coefficient
		Shake flask method
		Thin-layer chromatography (TLC)
		High-performance liquid chromatography (HPLC)
	Drug absorption, distribution and bioavailability
	Passive diffusion
	The pH partition hypothesis
		Limitations of the pH partition hypothesis
	Active transport mechanisms
	The action of local anaesthetics
	Excretion and reabsorption of drugs
	Food and drink
	Tutorial examples
	Problems
Physicochemical properties of drugs
	Carboxylic acids
	Phenols
	Warfarin
	Phenylbutazone
	Indometacin
	Barbiturates
	Phenytoin
	Sulfonamides
	Basic drugs
	Basicity of heterocyclic compounds
	Separation of mixtures
	Tutorial examples
	Problems
Stereochemistry
	Polarimetry
	Biological systems
	Fischer projections
		d and l configurations
		R and S configurations
		Molecules with more than one chiral centre
	Stereochemistry case study: thalidomide
	Geometrical isomerism
	Tutorial examples
	Problems
Drug metabolism
	Metabolic pathways
		Biotransformations
	Cytochromes P450
	Enzyme induction and inhibition
	Drug conjugation reactions (Phase 2)
		Glucuronic acid conjugation
		Sulfate conjugation
		Amino acid conjugation
		Miscellaneous conjugation reactions
	Stereochemistry
	Metabolic pathways for common drugs
	Tutorial example
	Problems
Volumetric analysis of drugs
	Volumetric flask
	Pipette
		Transfer (or delivery) pipettes
		Graduated pipettes
	Burettes
	Units of concentration
	Worked example
	Concentration of active ingredients
	Design of an assay
	Practical points
		Weighing by difference
		Approximate titre calculation
		Use of molarities in calculation
		Choice of indicators
	Back and blank titrations
		Results
	Assay of unit-dose medicines
	Non-aqueous titrations
	REDOX titrations
	Compleximetric titrations
	Argentimetric titrations
	Limit tests
	Problems
Analytical spectroscopy
	Effect of pH on spectra
	Instrumentation
		Light source
		Monochromator
		Detector
	Experimental measurement of absorbance
	Dilutions
		Worked example
	Quantitative aspects of spectroscopy
	Beer's and Lambert's laws
	Methods of drug assay
	Derivative spectroscopy
	Infrared spectroscopy
		Quantitative analysis using infrared spectroscopy
	Fluorimetry
		Quenching
	Structure elucidation
		Nuclear Magnetic Resonance (NMR)
			Instrumentation
			Solvents for NMR
			Internal standards
			Deuterium exchange
			Structure elucidation using NMR
			Chemical shift
			Integration
			Multiplicity and spin--spin coupling
		Mass spectrometry
	Tutorial examples
	Problems
Chromatographic methods of analysis
	Definitions used in chromatography
	Types of chromatography
		Paper chromatography
		Thin layer chromatography
		Column chromatography
		High performance liquid chromatography
			Pumps
			Injection systems
			Columns
			Packing materials and mobile phases
			Detectors
		Chiral chromatography
		Gas chromatography
			Head-space analysis
	Terms used in chromatography
	Tutorial examples
	Problems
Stability of drugs and medicines
	Oxidation
		Autoxidation
			Initiation
			Propagation
			Termination
		Stability of free radicals
		Prevention of oxidative deterioration
			Exclusion of oxygen
			Use of amber or coloured glass containers
			Use of chelating agents
			Use of antioxidants
		Autoxidation of fats and oils
		Ageing
	Hydrolysis
		Acid-catalysed hydrolysis
		Base-catalysed hydrolysis
		Examples of drugs susceptible to hydrolysis
			Aspirin
			Diamorphine
			Penicillin
	Other mechanisms of degradation
	Prodrugs
	Tutorial examples
	Problems
Kinetics of drug stability
	Rate, order and molecularity
	Rate equations and first-order reactions
	Half-life
	Shelf-life
	Second-order reactions
	Zero-order reactions
	Reaction rates and temperature
	Tutorial example
	Problems
Licensing of drugs and the  British Pharmacopoeia
	European licensing procedures
	Applications for marketing authorisations
	British Pharmacopoeia Commission
	The British Pharmacopoeia
Medicinal chemistry: the science of rational drug design
	How do drugs work?
		Enzyme inhibition
		Receptor activation/blocking
	Where do drugs come from?
	Why do we need new drugs?
		Existing drugs are not very good
		Existing drugs are no longer effective
		Appearance of `new' diseases
		`Unfashionable' diseases
Answers to problems
Selected bibliography
Index