Sodium benzoate. Caffeine-sodium benzoate Test questions and situational tasks
Laboratory work No. 5
Analysis of purine derivatives
Caffeine-sodium benzoate (Coffeinum – natrii benzoas)
Conclusion: the drug has its own physical properties meets the requirements of the Global Fund.
Authenticity:
Caffeine sodium benzoate
UV spectrometry
With general alkaloid precipitation reagents. With a 0.1% solution of tannin, a white precipitate is formed, soluble in excess of the reagent.
0.5 g of the drug is dissolved in 3 ml. water, add 1 ml. sodium hydroxide solution, 10 ml. chloroform and shake for 1-2 minutes. The chloroform layer is filtered through a filter with anhydrous sodium sulfate and the chloroform is evaporated in a water bath. The remainder gives the authenticity reaction to caffeine:
To 10 mg. Add 10 ml of hydrochloric acid and 0.5 ml of hydrogen peroxide to the preparation in a porcelain cup and evaporate to dryness in a water bath. Add 1 drop of ammonia - the precipitate acquires a purple-red color, which disappears when 2-3 drops of sodium hydroxide solution are added.
Murexide test for caffeine
Reaction to benzoate. K 2 ml neutral benzoate solution (0.01-0.02 g benzoate ion) add 0.2 ml ferric chloride solution; a pinkish-yellow precipitate is formed.
Sodium salt added to a colorless flame turns it yellow.
Transparency and color of the solution. Solution of 0.5 g of the drug in 10 ml water should be transparent and colorless
Alkalinity or acidity. 0.25 g of the drug is dissolved in 5 ml freshly boiled and cooled water and add a few drops of phenolphthalein solution. The solution should not turn pink. A pink color should appear from adding no more than 0.15 ml of 0.05 N. caustic soda solution.
Organic impurities. 0.3 g of the drug is dissolved in 3 ml of concentrated sulfuric acid. The color of the solution should not be more intense than standard No. 5a.
Chlorides. 0.1 g of the drug is dissolved in 5 ml of water, add 5 ml alcohol The resulting solution must pass the test for chlorides (no more than 0.02% in the preparation).
Sulfates. 0.5 g of the drug is dissolved in 5 ml of water, add 5 ml alcohol The resulting solution must pass the test for sulfates (no more than 0.02% in the preparation).
Heavy metals. 0.5 g of the drug is dissolved in 10 ml of water. The resulting solution must withstand the test for heavy metals(no more than 0.001% in the drug).
Weight loss during drying. About 0.5 g of the drug (exactly weighed) is dried at 80° to constant weight. Weight loss should not exceed 5%.
Quantitative determination of caffeine-sodium benzoate by kOpheine.
About 0.1 g of powder is dissolved in 10 ml of water in a 50 ml volumetric flask, 2 ml of diluted sulfuric acid and 8 ml of 0.1 mol/l iodine solution are added, the volume is adjusted to the mark with water and mixed. After settling for 15 minutes, the solution is quickly filtered through a layer of cotton wool into a dry flask, covering the funnel with a watch glass. The first 10 ml of filtrate is discarded. Transfer 25 ml of the filtrate into a flask and titrate the excess iodine with 0.1 mol/l sodium thiosulfate solution until discolored (indicator - starch).
At the same time, a control experiment is carried out by titrating the iodine solution after filtration (A ml).
1 ml of 0.1 mol/l iodine solution corresponds to 0.004855 g of anhydrous caffeine. The content of caffeine sodium benzoate (X) in grams is calculated using the formula:
where P is the average mass of the powder, g; 2.564 - conversion factor to caffeine-sodium benzoate with a caffeine content of 38 - 40% in the preparation.
Iodometry method. It is based on the formation of a precipitate of caffeine periodide in an acidic medium, which is filtered and excess iodine is determined in the filtrate.
Dana LF:
Caffeine sodium benzoate 0.05 g
Sugar 0.1 g
Conclusion:
Storage: former list B, in a well-closed container.
Application: CNS stimulant, cardiotonic.
1. To carry out analytical control of the substance caffeine-sodium benzoate:
· Give the chemical formula and rational name of caffeine-sodium benzoate. Justify it physical and chemical properties and propose their use in drug quality analysis.
·According to chemical structure and suggest properties possible methods for quantitative analysis of the medicinal substance and the proposed mixture.
caffeine sodium benzoate
Coffeinum-natrii benzoas
1,3,7 – trimethylxanthine with sodium benzoate
Caffeine-sodium benzoate is a white, odorless powder, slightly bitter taste, easily soluble in water, difficult in alcohol. A double salt obtained by mixing aqueous solutions containing 40% caffeine and 60% sodium benzoate.
Caffeine is a fully methylated derivative of xanthine (2,6-dioxypurine in 7H form).
Purine is a condensed heterocyclic system consisting of pyrimidine and imidazole rings. It is a tertiary base and undergoes oxidation and precipitation reactions.
Sodium benzoate is a salt formed by a strong base and a weak one. organic acid, characterized by displacement-precipitation reactions.
The inorganic components of the dosage form - NaBr and MgSO 4 - are medium salts, easily soluble in water. They enter into exchange reactions, forming insoluble precipitates (Na zincuranyl acetate, Na picrate, magnesium ammonium phosphate). Bromides enter into redox reactions, exhibiting restorative properties, precipitation reactions (with AaNO 3). Sulfates enter into precipitation reactions with barium salts.
Authenticity: - caffeine-sodium benzoate
1) Murexide test (GF X), is based on the destruction of the purine molecule at t with an oxidizing agent to form a mixture of methylated alloxan derivatives of idialuric acid, the interaction of which produces alloxanthin, which in an ammonia environment forms the ammonium salt of tetramethylpurpuric acid.
This reaction is used for substance analysis (after chloroform extraction)
2) In LF, caffeine is determined by the precipitation reaction with a solution of I 2 and the addition of HCI solution, a brown precipitate is formed.
3) sodium benzoate is determined by the complexation reaction with FeCI 3 (GF X)
6C 6 H 5 COONa +2FeCI 3 +10H2O → (C 6 H 5 COO) 3 Fe Fe(OH) 3 7H 2 O + 3C 6 H 5 COOH+ 6NaCI
1,3,7-trimethylxanthine monohydrate
Receipt:
2. Synthetically
a) Traube synthesis (for theophylline and caffeine):
Description: White silky needle-shaped crystals or white crystalline powder with a bitter taste, odorless.
Solubility: Slowly soluble in water, LR in hot, TP in alcohol. The solutions have a neutral reaction.
Authenticity:
1. Murexide test (oxidation in an acidic environment with destruction of the imidazole ring):
2. GF – UV spectrum, 1 maximum;
3. reaction with I 2: when adding a solution of I 2 to caffeine, there should be no sediment or turbidity, however, if we acidify the solution, a brown precipitate appears, Coff I 4 HI, soluble in NaOH
Coff + I 2 à no reaction à (on acidification) Coff I 4 HI¯, soluble in NaOH.
4. When tannin is added, a white precipitate is formed, soluble in excess of the reagent.
Non-GF:
1. MF - IR spectrum in comparison with the standard.
2. In an alkaline environment, the pyrimidine ring is destroyed:
3. Azo coupling reaction:
Purity:
1. Foreign alkaloids are unacceptable. The drug solution should not precipitate with Mayer's reagent.
2. Theobromine and theophylline are unacceptable. TLC. Only 1 spot is allowed on the chromatogram.
3. Organic impurities containing H 2 SO 4 – must be transparent and colorless.
Quantification:
1. Non-aqueous titration. Caffeine is dissolved in chloroform and acetic anhydride is added. The indicator is crystal violet, titrated to a yellow color.
2. Reverse iodometry (RF for caffeine-sodium benzoate):
Coff + I 2 + KI + H 2 SO 4 à Coff I 4 HI + KHSO 4
I 2 + 2Na 2 S 2 O 3 à Na 2 S 4 O 6 + 2NaI
Before titrating excess iodine, the precipitate must be filtered.
4. FEC (based on the reaction of azo dye formation).
Storage: List B. In a well-closed container.
Application: Caffeine (and caffeine sodium benzoate) is used for infectious and other diseases accompanied by depression of the functions of the central nervous system and cardiovascular system, in case of poisoning with drugs and other poisons that depress the central nervous system, with spasms of cerebral vessels (with migraines, etc.), to increase mental and physical performance, to eliminate drowsiness. Caffeine is also used for enuresis in children.
Authenticity.
Caffeine sodium benzoate
Coffeinum natrio-benzoicum
Receipt. The interaction of aqueous solutions of sodium benzoate and caffeine, the resulting solution is evaporated to form a dry powder.
1. reactions to caffeine after isolation with alkali and chloroform.
2. The reaction of benzoate ion with iron trichloride forms a flesh-colored precipitate.
3. the drug gives reactions characteristic of sodium ion.
1. determination of caffeine by the iodometric method after its precipitation from the preparation with acid in the form of caffeine base, the caffeine content should be 38 - 40% in terms of dry matter.
An exact weighed portion of the drug is dissolved in water, diluted sulfuric acid and a 0.1 M iodine solution are added, after settling for 15 minutes, the solution is filtered and the excess iodine in the filtrate is titrated with a 0.1 M sodium thiosulfate solution, and at the end of the titration a starch solution is added.
I 2 + 2Na 2 S 2 O 3 = 2NaI + Na 2 S 4 O 6
UC=1/4; back titration formula
2. In another sample, the amount of sodium benzoate is determined by the neutralization method. Titration is carried out in the presence of ether, which extracts the released benzoic acid.
An exact weighed portion of the drug is dissolved in water, ether and a mixed indicator (methyl orange and methylene blue) are added and titrated with 0.5 M hydrochloric acid until the water layer turns lilac.
Sodium benzoate should be 58 - 62%.
Storage. in a well-closed container.
Application. Central nervous system stimulant, cardiotonic.
Release forms. Solutions for injections 10, 20%, tablets 0.1; 0.2.
Cm. Educational and methodological manual on intrapharmacy control: concentrated solution of caffeine-sodium benzoate 10%; solutions for internal use- solution of sodium bromide and caffeine-sodium benzoate; infusion of adonis herb, caffeine-sodium benzoate and sodium bromide; in-pharmacy preparation and packaging (potion) of the composition: infusion of rhizomes and roots of valerian, caffeine-sodium benzoate, magnesium sulfate, sodium bromide, peppermint tincture.
sodium benzoas
C 7 H 5 NaO 2 M.w. 144.11
Description. White crystalline or amorphous powder, odorless or with a very slight odor.
Solubility. Easily soluble in water, moderately soluble in alcohol 90%, practically insoluble in ether and chloroform (GF XI, issue 1, p. 175).
Authenticity. Ultraviolet spectrum 0.001% aqueous solution The drug in the region from 220 to 300 nm has an absorption maximum at 226 nm ± 2 nm.
0.2 g of the drug in 2 ml of water gives a characteristic reaction to benzoates (SP XI, issue 1, p. 159).
Transparency of the solution. A solution of 1 g of the drug in 10 ml of freshly boiled and cooled water should be transparent or comparable with standard solution 1 (GF XI, issue 1, p. 198).
Color of the solution. A solution of 0.5 g of the drug in 5 ml of freshly boiled and cooled water should be colorless (GF XI, issue 1, p. 194).
Alkalinity and acidity. To the solution obtained in the “Transparency” test, add 0.1 ml of phenolphthalein. The color of the solution should change from adding no more than 0.2 ml of 0.1 M sodium hydroxide solution or 0.2 ml of 0.1 M hydrochloric acid solution.
Chlorides. 0.1 g of the drug is dissolved in 5 ml of water, 5 ml of 95% alcohol is added. The resulting solution must pass the test for chlorides (no more than 0.02% in the preparation; SP XI, issue 1, p. 165).
Sulfates. 0.5 g of the drug is dissolved in 4.5 ml of water, 5 ml of 95% alcohol and 0.5 ml of diluted hydrochloric acid are added. The resulting solution must pass the test for sulfates (no more than 0.02% in the preparation; SP XI, issue 1, p. 165).
Heavy metals. 0.5 g of the drug is dissolved in 5 ml of water, 5 ml of 95% alcohol is added. The resulting solution must pass the test for heavy metals (no more than 0.001% in the preparation; SP XI, issue 1, p. 165).
Weight loss during drying. About 0.5 g of the drug (exactly weighed) is dried at a temperature of 100 to 105 ° C to constant weight. The loss in mass should not exceed 2.0% (GF XI, issue 1, p. 176).
Quantification. About 1.5 g of the drug (exactly weighed) is dissolved in 20 ml of water in a flask with a ground stopper, capacity 250 ml, add 45 ml of ether, 0.2 ml of indicator and titrate with a 0.5 M solution of hydrochloric acid until a lilac color appears in aqueous layer. At the end of the titration, the contents of the flask are shaken well.
1 ml of 0.5 M solution of hydrochloric acid corresponds to 0.07205 g of C 7 H 5 NaO 2. The drug contains at least 99.0% g C 7 H 5 NaO 2 in terms of dry matter.
Note. Preparation of the indicator . 1 ml of 0.1% methyl orange solution is mixed with 1 ml of 0.15% methylene blue solution. The solution is used freshly prepared.
Storage. In a dry place, protected from light, at a temperature above + 25 0 C.
Test questions and situational tasks.
1. Explain the acidic properties of phenols from an electronic point of view.
2. What is the scope of application in pharmaceutical analysis of electrophilic substitution reactions of phenols? Give examples.
3. One of the chemical properties of phenols is their good oxidation with subsequent condensation of the initial and formed products. Give examples of reactions of this type with chloramine or bleach using phenol as an example, and with Marquis’ reagent (formaldehyde with concentrated sulfuric acid) using resorcinol as an example.
4. Give reaction equations for the combination of phenols with diazonium salt in an alkaline medium using phenol and resorcinol as an example.
5. Of the substitution reactions in pharmaceutical analysis, the ability of phenols to bromate and nitrate is used. What products are obtained? How can these reactions be used to confirm the identity of phenol derivatives? Give reaction equations using the example of sinestrol (bromination) and phenol (nitration).
6. The product of phenol nitration is used in pharmaceutical chemistry as a reagent. Write its formula, give its chemical and trivial names, as well as the reaction in which it acts as a reagent.
7. One of general reactions identification for phenolic hydroxyl is the reaction with ferric chloride. Name the type of reaction. Which of the following substances does not give this reaction: phenol, menthol, resorcinol, thymol.
8. To test the authenticity of resorcinol, the State Fund of X recommends the fluorescein formation reaction. Write the equation of the reaction, name its type and stages.
9. Justify the iodine and iodochlorometric methods for analyzing resorcinol. What will be the equivalence factor of the drug?
10. What chemical properties of vikasol are used in cerimetric and iodometric methods of quantitative determination.
11. Chemical properties aromatic acids and their salts.
12. Methods for producing aromatic acids and their derivatives.
13. General and specific methods for identifying drugs of this group.
14. General and specific methods of quantitative determination.
15. Storage conditions of the drug depending on the chemical composition.
16. Justify the pharmacopoeial method for the quantitative determination of sodium benzoate. For what purpose is the determination carried out in the presence of ether? Give equations, derive the equivalence factor.
17. Quantitative Analysis sodium benzoate according to the pharmacopoeial method is carried out using the acidimetric displacement method. Calculate the titer if a solution of hydrochloric acid (0.5 mol/l) is used as the titrated solution.
18. Make a conclusion about the quality of thymol if, according to the GF method, 13.0 ml of potassium bromate solution (0.1 mol/l, UC 1/6 KBrO 3) was consumed to titrate a sample of 0.1501 g.
19. Calculate the mass of powdered vikasol tablets so that 22.5 ml of cerium (IV) sulfate solution (0.1 mol/l, UC 1/2 Ce(SO 4) 2) is consumed for titration using the GF method. The average tablet weight is 0.1014 g.
20. What portion of resorcinol should be taken so that when determining by the iodochlorometric method, 10 ml of sodium thiosulfate (0.1 mol/l) is used for the back titration of the released iodine, the volume of iodine monochloride is 30 ml (0.1 mol/l, UC ½ ICl) .
List of literature for preparation.
1. Belikov, V.G. Pharmaceutical chemistry: Textbook. For universities. – Pyatigorsk, 2003. P. 258-266.
2. Pharmaceutical chemistry: Textbook. Manual / Ed. A.P. Arzamastseva. – 2nd ed., rev. – M.: GOETAR-Media, 2005.
3. Chemical analysis medicinal substances By functional groups. Educational and methodological manual for students of the Faculty of Pharmacy. – Nizhny Novgorod: Publishing House of the Nizhny Novgorod State medical academy, 2003.
4. Organic medicines. Aromatic compounds. Brief summary lectures. – Nizhny Novgorod: Publishing House of the Nizhny Novgorod Medical Academy, 2004.