MC1 Separation Techniques for Drugs

MC1 Separation Techniques for Drugs – Report

1)      COSHH

Hazards Identification of Chemicals MSDS   (Fisher Scientific 2011)

Cholesterol: Slightly hazardous in the case of indigestion, skin contact (irritant, permeator), eye contact and inhalation.

Benzoic Acid: Slightly hazardous in case of indigestion, skin contact (permeator), eye contact (irritant) and inhalation.

2M Hydrochloric Acid: Causes severe burns and eye damage. Vapours must not be inhaled.

1M Sodium Hydroxide: Causes severe burns and eye damage.

Ethyl Acetate: Slightly hazardous in the case of indigestion, skin contact (irritant, permeator), eye contact and inhalation.

Sodium Sulfate: Can cause skin irritation

Safety goggles must be worn at all times to prevent damage to the eye. Chemical substances can get into the eye and cause irritation. During the partitioning and crystallisation, the following chemicals cause irritation to the eye: Benzoic Acid, Cholesterol, 2M Hydrochloric Acid, 1M Sodium Hydroxide and Ethyl Acetate. Flush eyes immediately with plenty of warm water for a minimum of 15 minutes if chemical contact has been made.

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Nitrile gloves must be worn at all times to prevent damage to the skin. Chemical substances can make contact with the skin whilst performing the partitioning and crystallisation. The gloves must be removed appropriately. In incidence of contact, immediately flush skin with water and cover the skin with emollient. Replace gloves if any chemical contact has been made. The following chemicals are hazardous to the skin: Benzoic Acid, Cholesterol, 2M Hydrochloric Acid, 1M Sodium Hydroxide, Ethyl Acetate and Sodium Sulfate.

A Howie style lab coat must be worn at all times and is not to be removed until after all chemicals have been put away and the experiment has completely finished. The lab coat must be buttoned all the way to the top to prevent chemical substances making contact with the skin. The following chemicals are hazardous to the skin: Benzoic Acid, Cholesterol, 2M Hydrochloric Acid, 1M Sodium Hydroxide, Ethyl Acetate and Sodium Sulfate.

The chemicals should not be inhaled or ingested at any point during the partitioning and crystallisation. No eating or drinking is permitted in the laboratory due to the risk of contamination.  If a substance is swallowed/inhaled, rinse mouth with water and seek medical attention.

Rotary evaporators should be sheathed with a coating or netting made of nylon to minimise breakage of glass through implosion.

A tea towel must be used when handling the watch glass after drying the benzoic acid in the oven and when using the hot filtration apparatus. This prevents skin burns.

During the solvent extraction, the 2M Hydrochloric Acid and 1M Sodium Hydroxide must be dispensed from an acid-base dispenser contained within a fume cupboard. This reduces the risk of hazardous chemical substances from spilling as they are kept safely away from the workspace. The piston mechanism of the dispenser must never be forced if it is difficult to move. Seek help from technical staff instead.

When operating the separating funnel, a stopper must be used. When shaking, the funnel must be inverted. This creates a build-up of pressure which must be vented through the tap between shakes to avoid explosion. The separating funnel must be pointed away from peers during this procedure.

Broken glass material must be disposed of in the glass bin. Gloves must be disposed of in the yellow glove bins

2)      Experimental Results

Melting Point / °C

Cholesterol

Melting Point / °C

Benzoic Acid

Partitioning

142-153

120-127

Crystallisation

 112-117

122-124

Literature

147 – 150

121-125

Mass of benzoic acid/cholesterol (4:1) mixture / g

% Recovery

Cholesterol

% Recovery

Benzoic Acid

Partitioning

1.99:0.67

111

83

Crystallisation

2.57:0.81

135

107

Literature values taken from: Human Metabolome Database (2018) and ICSC 0103 (2018)

Calculations:

Mass of benzoic acid and cholesterol

3.00g of benzoic acid/cholesterol mixture      

(3 ÷ 5) x 4 = 2.40g (benzoic acid)

3.00g – 2.40 = 0.60g (cholesterol)

% Recovery Cholesterol

Partitioning: (0.67÷0.60) x 100 = 111%

Crystallisation: (0.81÷0.60) x 100 = 135

%Recovery Benzoic Acid

Partitioning: (1.99÷24) x 100 = 83%

Crystallisation: (2.57÷2.4) x 100 = 107%

3)      Data Analysis

Q1) Benzoic acid contains an ionisable carboxylic acid group. Once sodium hydroxide is added, an acid base reaction takes place creating sodium benzoate, which is very hydrophilic. The ionised molecule is now able to form hydrogen bonds with water more readily and becomes part of the aqueous solution. Upon shaking the separating funnel, two immiscible solutions are formed. The aqueous solution is removed leaving behind the insoluble cholesterol solution. The melting point for benzoic acid after solvent extraction ranged from 120°- 127° which is similar to the literature value of 121 – 125°. However, it is quite a large range and the melting point is slightly lower than the literature value which suggests the benzoic acid contains small amounts of impurities. The difference in melting point however is very minimal (-1) and could be a result of human error. The recovery percentage for benzoic acid was 83% which is below 100%. This means 17% of the product was either lost during the procedure or is impure. This could be due to an error during solvent extraction. It is possible that not all the benzoic acid reacted with the sodium hydroxide so insufficient sodium benzoate was produced. This could be due to an error when shaking and inverting the separating funnel. During the isolation by suction filtration, it is possible that not all crystals were washed out. This could’ve resulted in lost product. Another explanation for the low recovery percentage is that not all the aqueous solution was removed from the separating funnel. It is really difficult to differentiate the two layers with the human eye so tiny amounts of the aqueous solution may have stayed in the funnel causing product to be lost whilst leaving impurities in the remaining layer.

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For crystallisation, the melting point ranged from 122° – 124° which is within the literature value range. Benzoic acid is insoluble in cold water. Heat is required in order for it to go into solution. Once heated, the hydrophilicity of benzoic acid increases allowing it to form hydrogen bonds with water and to become part of one solution. The hydrophilicity increases with heat because more energy is available to accelerate the dissociation of benzoic acid making it more soluble. The range is a lot smaller when compared to the solvent extraction melting point range and both melting point values are within the literature range which means the sample is pure. However, the recovery percentage of crystallisation was 107%. This value is greater than 100% which means none of the product was lost however it does indeed contain some impurities. Contaminate does adhere to the crystals of the product as they precipitate, which can give an impure product. Finally, too much solvent could have been used accidently, so less of the compound is recrystallized and remains in the solution. Overall, both values suggest that crystallisation is the better separating technique as it contained less impurities than solvent extraction and didn’t result in any lost product.

Cholesterol is very lipophilic. It only dissolves in lipids or fats. It does not contain any ionisable groups (under the conditions used) and has no capacity to form hydrogen bonds leaving it insoluble in cold and hot water (hydrophobic). The melting point for cholesterol after solvent extraction ranged from 142°- 153° which is similar to the literature value of 147 – 150°. However, it is a large range and the melting point is 5°C lower than the literature value which suggests the cholesterol contained small amounts of impurities. The recovery percentage for cholesterol was 111%. Since the value is above 100%, it means none of the product was lost but 11% of the product was impure. This could be due to the amount of human error involved during the extraction of cholesterol. Small amounts of benzoic acid could’ve remained in the separating funnel when removing the aqueous layer.

During the crystallisation, cholesterol never went into solution due to its lipophilic properties so as a result, even after heating the water, it remained undissolved. Crystallisation gave a melting point of 112°C – 117°C which is 35°C lower than the literature value. The recovery percentage was 135%. Both sets of data show that this technique gave a lot of impurities. The reason for this could be due to contamination when drying the cholesterol. The filter papers used when drying were very dirty and the direct contact when layering, transferred impurities on to the cholesterol crystals. It is also possible that small amounts of water made contact with cholesterol instead of ethyl acetate during the washing. If this wasn’t the case, the crystallisation technique would’ve given a purer product but based on the data and due to the error in drying, solvent extraction gave the purer product for cholesterol.

4)      Medicinal Chemistry Questions

Q3)

Q4) Benzoic acid is used as a preservative in food due to its ability to prevent the growth of microbes.

Q5)                                                                                                   Q)6

Q7) High levels of cholesterol in the blood can cause coronary heart disease and other cardiovascular diseases, such as stroke. This is due to the accumulation of cholesterol in the arteries. This blocks blood flow to the heart and consequently oxygen supply. This results in the heart being unable to respire causing cells to die. (Terms 2013)

Q8)Statins are used to lower the cholesterol level in your blood. Statins act as a substrate for the Organic Anion Transporting Polypeptide (OATP) transporter. This transporter is responsible for the transcellular movement of statin drugs inside the hepatic cell. Through this, statins competitively inhibit HMG CoA enzyme reductase within the liver cell which leads to an inactivation of Mevalonic acid production from the HMG Co-enzyme A form into cholesterol. The consequence reduces cholesterol production. (Stancu and Sima 2001)

Q9)

 

 

1 Nitrogen chiral centres and 2 Carbon centres

Functional groups: Halide, Phenyl, Alkene, Hydroxy, Carboxylic Acid, Amine, Pyridine, Methyl and Sulphonamide

Bibliography

Fisher Scientific. (2011). Cholesterol MSDS. [online]. Available from: https://online.manchester.ac.uk/bbcswebdav/pid-6165454-dt-content-rid-25976935_1/courses/I3116-PHAR-10100-1181-1YR-028141/Cholestrol.pdf [Accessed November 25, 2018].

Stancu, C. and Sima, A. (2001). Statins: Mechanism of action and effects. Journal of Cellular and Molecular Medicine, 5(4), pp.378–387. [online]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12067471 [Accessed November 27, 2018].

Terms, R. (2013). High cholesterol. , 2013, pp.1–53. [online]. Available from: https://www.nhs.uk/conditions/high-cholesterol/ [Accessed November 27, 2018].

Human Metabolome Database (HMDB). Cholesterol. [online]. Available from: http://www.hmdb.ca/metabolites/HMDB0000067[Accessed November 25, 2018].

ICSC 0103 – BENZOIC ACID. [online]. Available from: http://www.ilo.org/dyn/icsc/showcard.display?p_version=2&p_card_id=0103 [Accessed November 25, 2018].