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 (usually synthetic) in sport as they function as performance-enhancing drugs. Steroids: lipid molecules (e.g. testosterone, cholesterol) that have 4 fused rings that have 17 carbons (steroidal backbone) – functional groups differ

3. Steroids Anabolic steroids promote muscle growth
Example: testosterone (natural) nandrolone (synthetic form testosterone)

4. Detection of steroids in sport
Gas chromatography - GC
Mass spectrometry

5. Gas chromatography – GC-MS
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 (= retention time) at which it passes through the stationary phase

6. 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.

7. Gas chromatography apparatus

8. Gas chromatography
The retention times (time it takes to be eluted) for a variety of compounds are known and the component can therefore be identified
Retention time depends on the boiling point of the substance, its solubility in the liquid (stationary) and gas (mobile) phase and the temperature of the oven
On their way through substances will spend time dissolved in the liquid phase and carried along by the mobile phase
Identification can also be completed using the fragmentation pattern obtained using mass spectrometry (=more accurate): GC-MS !!!

9. Gas chromatogram: identification
Area under peak indicates concentration of X relative to standard S

10. Gas chromatography: retention index – RI

11. GC-MS
This technique uses both gas chromatography and mass spectrometry to detect the presence of banned substances such as steroids

12. 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.

13. 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.

14. 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

15. Solvent extraction
Refers to the process in which a suitable solvent is selected that dissolves the target organic compound (=solute) to be extracted or isolated from a solution.
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 (the solute is present in 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.

16. Solvent extraction: liquid-liquid
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 (re) crystallization

17. Fractional distillation: main ideas
Vapour pressure of a pure substance = pressure when the vapour phase is in equilibrium with its liquid phase.
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.

18. 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, e.g. 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 in solution= moles of A/moles of A + B.
Mole fraction B = moles of B/moles of A + B.

19. 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

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

21. Fractional distillation: main ideas

22. Detection of ethanol: breathalyser
Ethanol is sufficiently volatile to pass into the lungs from the bloodstream so can be detected using a breathalyzer which contains acidified potassium dichromate(VI), an oxidizing agent.
Direct relationship between the alcohol content in exhaled air and the alcohol content in the blood.
In a positive result 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 = -2 ) 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.

23. Detection of ethanol: breathalyser
Oxidation
C2H5OH + H2O → CH3COOH + 4H+ + 4e−
Reduction
Cr2O7 2− H+ + 6e− → 2Cr3+ +7H2O
Overall
3C2H5OH+16H+ +2Cr2O72− → 3CH3COOH+2Cr3++ 11H2O

24. Detection of ethanol in breath: intoximeter using a fuel cell
Cell = 2 platinum electrodes and an acid electrolyte; uses electrochemistry.
Breath is passed over cell.
Anode: C2H5OH + H2O → CH3COOH + 4H+ + 4e-
Cathode: O2 + 4H+ + 4e- → 2H2O
Current flows from anode (ox) to cathode (red)
Overall: C2H5OH + O2 → CH3COOH + H2O
The voltage of the current can be used to measure the ethanol concentration.

25. 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