1. Drug detection and analysis
Essential idea
A variety of analytical techniques is used for detection, identification, isolation and analysis of medicines and drugs.

2. Drug detection
IR, mass spectrometry and 1H NMR can be used to detect banned or illegal chemicals such as steroids (hormones) in sport as they function as performance-enhancing drugs. Steroids: lipids found in sex hormones (e.g testosterone) that promote muscle growth (anabolic steroids). Examples: nadrolone.

3. Detection of steroids in sport
Gas chromatography
Mass spectrometry

4. Gas chromatography
Used to separate and identify the components in a mixture such as blood and urine.
Relies on the different components in the mixture having different affinities for two different phases, a mobile phase (a gas medium) and a stationary phase (made up of a liquid).
The different affinities depend on its boiling point/volatility and its solubility in both the gas and the liquid
Affinities determine the rate at which it passes through the stationary phase.

5. Gas chromatography: how?
The mixture sample is heated (boiling point) and mixed with the gas phase (solubility) and injected in the gas chromatography column.
Each component travels though the column at a rate depending on their volatility and solubility in both phases (affinity). The components partitions itself between both phases.
A detector measures the time - retention time - this is the amount of time between injection time (t=0 on the gas chromatogram) and the time a component is eluted (=removed or extracted using a solvent).
The retention time of a component is recorded as a peak on the gas chromatogram.
The area underneath the peak indicates the concentration of the component.

6. Gas chromatography apparatus

7. Gas chromatography
The retention times for a variety of compounds are known and the component can therefore be identified although identification can also be completed using the fragmentation pattern obtained using mass spectrometry (=more accurate). (see 11.3)

8. Gas chromatogram

9. Gas chromatography

10. Extraction and purification
Many synthesis reactions in the pharmaceutical industry produce a mixture that contains the drug but often also excess or unreacted reactants and solvent. The next step is then to isolate or extract the drug from the mixture and increasing its purity.
Often the extraction and purification use differences in solubility in different solvents and/or volatility between the product and other substances in the mixture.

11. Organic structure and solubility
Polarity of the structure of molecules determines their solubility in polar and non-polar solvents.
Non-polar molecules have very low solubility in polar solvents such as water but higher solubility in other non-polar solvents. (London forces interactions)
Molecules with a polar structure and ionic compounds (salts) are very soluble in water (ionic, dipole-dipole, hydrogen bonding interactions) but have low solubility in non-polar solvents. The longer the carbon chain, the less the effect of the polarity, the lower the solubility.
Molecules that can hydrogen bond have the highest solubility in polar solvents.

12. Organic structure and solubility
low solubility
(non-polar molecules)
soluble
(dipoles)
high solubility
(hydrogen bonding)
alkanes/alkenes
aldehydes/ketones
alcohols
carboxylic acids
halogenoalkanes
amines/amides

13. Solvent extraction
Solvent extraction refers to the process in which a suitable solvent is selected that dissolves the organic compound (=solute) to be extracted or isolated from a solution.
The solvent used to extract the drug (e.g. cyclohexane if the drug is a non-polar molecule in an aqueous solvent) is immiscible with the solvent in which the solute is in (e.g. water).
The solute is partitioned between both solvents but a lot more in one than in the other. In the case of organic compounds usually more soluble in non-polar solvent.

14. Solvent extraction Example:
Extraction of penicillin using trichloromethane.
A separating funnel is used to remove the most dense solvent layer and the solute or drug can be obtained pure by crystallization

15. Fractional distillation: main ideas
Vapour pressure refers to the pressure when a vapour is in equilibrium with a liquid or solution.
The weaker the intermolecular forces, the more volatile a compound, the lower its boiling point, the higher its vapour pressure.
Raoults’ law applies to ideal solutions and states that the partial vapour pressure of each component in a solution is equal to the product of the vapour pressure of that component when pure multiplied by the mole fraction of that component in the solution.
Ideal solution = completely miscible liquids that behave in the same way as when they are pure e.g. in terms of vapour pressure, e.g. octane and hexane.

16. Fractional distillation: main ideas
This means that the total vapour pressure of a solution is equal to sum of the partial pressure of each component. For a solution consisting of 2 components A and B:
Ptotal = PA + PB
Partial pressure of PA = vapour pressure A when pure x mole fraction A in solution.
Partial pressure of PB = vapour pressure B when pure x mole fraction B in solution.
Mole fraction A = moles of A/moles of A + B.
Mole fraction B = moles of B/moles of A + B.

17. Fractional distillation: main ideas
Graph from your book shows Raoult’s law. It shows the vapour pressure of a solution of 2 components of different compositions.
Component B is more volatile as it has a higher vapour pressure

18. Fractional distillation: main ideas
Component B is the more volatile, has a higher vapour pressure and a lower boiling point.

19. Fractional distillation: main ideas

20. Detection of ethanol: breathalyser
Only used for detection of ethanol in breath.
Ethanol is sufficiently volatile to pass into the lungs from the bloodstream which is why it can be detected using a breathalyzer which contains acidified potassium dichromate(VI), an oxidizing agent.
There is a direct relationship between the alcohol content in exhaled air and the alcohol content in the blood.
In a positive result (i.e. presence of ethanol) the potassium dichromate changes form orange (Cr (VI) or +6) to green (Cr (III) or +3) as the chromium in the chromate ion is reduced by the ethanol (C = ) and the ethanol itself oxidized to ethanal (C= -1) and ethanoic acid (C=0) .
The extent of the colour change corresponds to a particular ethanol concentration.

21. Detection of ethanol: breathalyser
Symbol equations:
oxidation:
C2H5OH + H2O → CH3COOH + 4H+ + 4e−
reduction:
Cr2O7 2− H+ + 6e− → 2Cr3+ +7H2O
Overall:
3C2H5OH+16H+ +2Cr2O72− → 3CH3COOH+2Cr3++ 11H2O

22. Detection of ethanol in breath: fuel cell
Cell = 2 platinum electrodes and an acid electrolyte; uses electrochemistry.
Breath is passed over cell.
Ethanol is oxidized to ethanoic acid and H2O at the anode releasing electrons that produce an electrical current between the electrodes.
At cathode oxygen reduced to water.
Overall equation: C2H5OH + O2 → CH3COOH + H2O
The voltage of the current can be used to measure the ethanol concentration.

23. Detection of ethanol in breath using a fuel cell: reactions
Anode:
C2H5OH(g) + H2O(l)→ CH3COOH(l) + 4H+(aq)+ 4e–
Cathode:
O2(g) + 4H+(aq) + 4e– → 2H2O(l)
Current flows from anode to cathode