Sodium benzoate. Quantitative chemical analysis of a substance

Gross formula

C8H10N4O2

Pharmacological group of the substance Caffeine

Nosological classification (ICD-10)

CAS code

58-08-2

Characteristics of the substance Caffeine

Pharmacology

Pharmacological action - analeptic, cardiotonic, psychostimulant.

Has a direct stimulating effect on the central nervous system: regulates and enhances excitation processes in the cerebral cortex, respiratory and vasomotor centers, activates positive conditioned reflexes And motor activity. Stimulates mental activity, increases mental and physical performance, shortens reaction time. After administration, vigor appears, fatigue and drowsiness are temporarily eliminated or reduced. Causes increased and deepening of breathing, especially against the background of depression of the respiratory center. Affects the cardiovascular system: increases strength and heart rate (especially in large doses), increases blood pressure during hypotension (does not change normal). Dilates the bronchi, biliary tract, blood vessels skeletal muscles, heart, kidneys, constricts - organs abdominal cavity(especially when they are dilated). Reduces platelet aggregation. It has a moderate diuretic effect, mainly due to a decrease in the reabsorption of electrolytes in the renal tubules. Stimulates the secretion of gastric glands. Increases basal metabolism, enhances glycogenolysis, causing hyperglycemia.

Blocks central and peripheral adenosine receptors. Promotes the accumulation of cAMP and cGMP by inhibiting the activity of phosphodiesterases involved in their inactivation. To a greater extent inhibits cAMP phosphodiesterase (not only in the central nervous system, but also in the heart, smooth muscle organs, adipose tissue, skeletal muscles). Stabilizes transmission at dopaminergic synapses (psychostimulating properties), beta-adrenergic synapses of the hypothalamus and medulla oblongata (increased tone of the vasomotor center), cholinergic synapses of the cortex (activation cortical functions) and medulla oblongata (excitation of the respiratory center), noradrenergic synapses (increasing physical activity, anorexia).

Caffeine and its water-soluble salts are well absorbed in the intestine (including the colon). T1/2 is about 5 hours, in some people - up to 10 hours. The main part is demethylated and oxidized. About 10% is excreted unchanged by the kidneys. In the body of full-term newborns and infants(1.5-2 months) is eliminated more slowly (T 1/2 - from 80 to 26.3 hours, respectively).

Impact on higher education nervous activity highly dependent on dose and type nervous system patient. In small doses the stimulating effect predominates, in large doses the depressant effect predominates. In older people, the effect on sleep is more pronounced: its onset slows down, the total time of sleep decreases, and the frequency of awakenings increases (possibly due to faster metabolism of catecholamines in the central nervous system). In premature infants, when eliminating periodic breathing, caffeine reduces the partial pressure of carbon dioxide, the concentration of H + in the blood and at the same time increases the volume of ventilation without changing heart rate.

Use of the substance Caffeine

Diseases accompanied by depression of the central nervous system, cardiovascular and respiratory systems(including drug poisoning, infectious diseases), cerebral vascular spasms (including migraine), decreased mental and physical performance, drowsiness, enuresis in children, breathing disorders (periodic breathing, idiopathic apnea) in newborns (including premature infants).

Contraindications

Expressed arterial hypertension, organic diseases cardiovascular system(including atherosclerosis), increased excitability, glaucoma, sleep disorders, old age.

Side effects of the substance Caffeine

Anxiety, agitation, insomnia, tachycardia, arrhythmias, increased blood pressure, nausea, vomiting. At long-term use Possible slight addiction (a decrease in the effect of caffeine is associated with the formation of new adenosine receptors in brain cells). Sudden cessation of caffeine administration may lead to increased central nervous system inhibition with symptoms of fatigue, drowsiness and depression.

Interaction

Reduces the effect of sleeping pills and narcotics, increases (improving bioavailability) - acetylsalicylic acid, paracetamol and others non-narcotic analgesics. Improves the absorption of ergotamine in the gastrointestinal tract.

Overdose

If abused, caffeine (more than 300 mg per day, i.e. four cups of natural coffee, 150 ml each) can cause anxiety, restlessness, tremor, headache, confusion, cardiac extrasystoles. In newborns (including premature infants), at a blood plasma concentration of 50 mg/ml, toxic effects are possible: anxiety, tachypnea, tachycardia, tremor, increased Moro reflex, and at higher concentrations - convulsions.

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Student research work

Quantitative chemical analysis of a substance. Sodium benzoate

Completed:

student of group 5201 KSMU

Mamedova S.N.

Checked by: Bukhovets A.V.

Kazan, 2014

Content

  • I. Analysis of the drug "Sodium benzoate"
  • II. Quantitative analysis of the drug "Sodium Benzoate" by direct acidimetry with a solution of 0.05 N. hydrochloric acid
  • III. Protocol for performing a titrimetric analysis of a sodium benzoate preparation by direct acidimetry with a solution of 0.05 N. hydrochloric acid in the presence of ether
  • Literature used

I. Analysis of the drug "Sodium benzoate"

1. RussianNamemedicinalfunds.

Sodium benzoate

Sodium benzoic acid

Sodium benzoic acid

Sodium benzoate

2. LatinNamemedicinalfunds.

sodium benzoas

Natrium benzoicum

3. ChemicalformulaWithindicatingmolarmasses

C6H5COONa

Molarweight 144,11

4. Externalview

White crystalline powder, odorless or with a very faint odor, sweetish-salty taste.

5. PhysicalAndchemicalproperties

Density: 1.44 g/cm 3

Solubility.

Easily soluble in water, difficultly soluble in alcohol.

TransparencyAndchromaticitysolution.

A solution of 1 g of the drug in 10 ml of freshly boiled and chilled water should be transparent and colorless.

AlkalinityAndacidity.

A few drops of phenolphthalein solution are added to the resulting solution; the solution should remain colorless. A pink color should appear from adding no more than 0.75 ml of 0.05 N. caustic soda solution.

Contentchlorides.

0.15 g of the drug is dissolved in 14 ml of water, add 1 ml of diluted nitric acid and filtered. 10 ml of the filtrate must pass the chloride test (not more than 0.02% in the preparation).

Contentsulfates.

1.5 g of the drug is dissolved in 25 ml of water, 5 ml of diluted hydrochloric acid is added and filtered. 10 ml of the solution must pass the test for sulfates (no more than 0.02% in the drug).

Contentheavymetals.

10 ml of the same filtrate must pass the test for heavy metals (no more than 0.001% in the preparation).

LossVweightatdrying.

About 1.5 g of the drug (exactly weighed) is dried at 100-105 to constant weight. Weight loss should not exceed 3%.

Humidity: no more than 2%.

Note . Sodium benzoate for the preparation of injection solutions must additionally pass a test for iron: a solution of 0.4 g of the drug in 10 ml of water must pass the test for iron (no more than 0.0075% in the drug).

6. Methodsreceiving

Sodium benzoate is obtained by the reaction of benzoic acid with a solution of sodium hydroxide or sodium carbonate:

a) with sodium hydroxide:

sodium benzoate chemical analysis

b) with sodium carbonate:

2+ Na 2 CO 3 2 + H 2 O + CO 2

7. Qualitativeanalysis

The drug gives a characteristic reaction to benzoates and reaction B to sodium.

High qualityreactiononbenzoates:

To 2 ml of a neutral benzoate solution (0.01-0.02 g of benzoate ion) add 0.2 ml of ferric oxide chloride solution; a pinkish-yellow precipitate is formed.

6C 6 H 5 COONa + 2FeCl 3 + 10H 2 O (C 6 H 5 COO) 3 Fe Fe(OH) 3 7H 2 O + 6NaCl + 3C 6 H 5 COOH

High qualityreactiononionssodium:

a) Dry reaction. Sodium salt added to a colorless flame turns it yellow.

b) With zinc acetate: (a yellow crystalline precipitate forms)

Na + +Zn [ (UO 2) 3 (CH 3 COO) 8 ] +CH 3 COOH + 9H 2 O = NaZn [ (UO 2) 3 (CH 3 COO) 9 ] 9H 2 O + H +

c) With a solution of picric acid (a yellow crystalline precipitate forms)

C 6 H 2 (NO 2) 3 OH + Na + > C 6 H 2 (NO 2) 3 ONa + H +

Methodologydefinitionsauthenticityaccording toStatePharmacopoeiaX:

0.25 g of the drug is dissolved in 5 ml of water, 1 ml of nitric acid is added, the separated white crystals are filtered off, washed with water and dried in a desiccator over sulfuric acid until a constant weight is achieved. The temperature of the resulting benzoic acid is 120-124.5°C.

Schemereactions:

C 6 H 5 COONa + HNO 3 C 6 H 5 COOH + NaNO 3

8. Quantitativeanalysis

About 1.5 g of the drug (exactly weighed) is dissolved in 20 ml of water in a flask with a ground stopper with a capacity of 250 ml, add 45 ml of ether, 3-4 drops of a mixed indicator (1 ml of methyl orange solution and 1 ml of methylene blue solution) and titrate 0.5 n. with a solution of hydrochloric acid until a lilac color appears in the aqueous layer. At the end of the titration, the contents of the flask are shaken well.

1 ml 0.5 n. hydrochloric acid solution corresponds to 0.07205 g of sodium benzoate, which in terms of dry matter must be at least 99.0%.

9. Application

1 . Preparation: Sodium benzoate

Pharmacologicalgroup: secretolytics and stimulants of motor function of the respiratory tract.

As an expectorant - alone (per se) and as part of combination drugs. When taken orally, it increases the secretion of the respiratory tract mucosa.

2 . Preparation: Caffeine sodium benzoate

Pharmacologicalgroup: respiratory stimulants, psychostimulants

Diseases accompanied by depression of the central nervous system, functions of the cardiovascular and respiratory systems (including drug poisoning, infectious diseases), cerebral vascular spasms (including migraine), decreased mental and physical performance, drowsiness, enuresis in children, breathing disorders (periodic breathing, idiopathic apnea) in newborns (including premature infants).

10. Termsstorage

In a well-closed container, in a dry place, protected from light.

II. Quantitative analysis of the drug "Sodium Benzoate" by direct acidimetry with a solution of 0.05 N. hydrochloric acid

1 . Essencemethod.

Selected method quantitative analysis sodium benzoate preparation is a direct acidometric titration and belongs to the acid-base titration methods.

Acid-basetitration- titrimetric methods for determining the concentration of acids or bases, based on the neutralization reaction: H 3 O + + OH? = 2H 2 O. Titration with an alkali solution is called alkalimetry, and titration with an acid solution is called acidimetry. In the quantitative determination of acids - alkalimetry - the working solution is a solution of a strong acid (usually HCl or H 2 SO 4). In the quantitative determination of alkali - acidimetry - the working solution is an alkali solution NaOH or KOH. It is impossible to prepare a titrated acid solution from concentrated acid.

If a solution of any acid is titrated with an alkali solution, the H + ions of the acid are bound by OH - ions and the concentration of H + ions gradually decreases, and the pH of the solution increases. At a certain pH value, the equivalence point is reached and the titration must be completed. When titrating an alkali solution with an acid solution, OH - ions bind, their concentration in the solution decreases, and the concentration of H + ions increases and the pH of the solution decreases. However, the pH value at the equivalence point does not have the same value in all cases; it depends on the nature of the reacting acid and base.

2 . Titrant,standardizationtitrant.

In the chosen titration procedure, the titrant is 0.05 N. HCl solution.

It is impossible to prepare a titrant using an exact sample, because hydrochloric acid is volatile. A solution of approximately the required concentration is prepared and standardization is carried out according to the setting substances: sodium tetraborate (borax) - Na 2 B 4 O 7 10H 2 O, anhydrous sodium carbonate - Na 2 CO 3, etc.

Preparationsolutiontitrantapproximatelynecessaryconcentrations:

a) calculate the mass of the substance to prepare the solution,

b) weigh the substance on an analytical balance,

c) the weighed substance is dissolved in a volumetric flask,

d) calculate the exact concentration of the solution,

e) calculate the correction factor.

Preparationsolutioninstallationsubstances:

The solution of the setting substance is prepared in the same way as preparing a titrant solution using an accurate weighing.

Requirements,presentedToinstallationsubstances:

a) the composition of the substance must correspond to the formula,

b) the substance must be pure,

c) the substance must be highly soluble in water,

d) the substance must be stable during storage as in pure form, and in solution,

e) the establishing substance must react with the titrant quickly and in stereochemical quantities (according to the reaction equation).

f) no side reactions should occur in the solution,

g) the installation substance must have a larger equivalent molar mass (less weighing error),

h) it should be possible to select an indicator.

i) standardization - the process of finding the exact concentration of a solution.

The accuracy with which the concentration of a standardized titrant is known limits the accuracy of the method as a whole, so attention is paid to the preparation of standard solutions special attention. The concentration of standard solutions is determined either directly (if the substance itself is the primary standard), or indirectly, if the substance does not meet the requirements for primary standards. In the first case, a carefully weighed amount of the substance is taken and diluted to an accurately known volume. In the second case, a solution containing a carefully weighed amount of the substance is titrated with a solution of the primary standard. Substances that can be considered as good primary standards must have a number of important properties: have high degree purity, be resistant to atmospheric influences, have low hygroscopicity and low tendency to weathering, be easily accessible, and have a sufficiently high equivalent mass. Few substances satisfy these requirements, so the number of primary standards is very limited.

Primary standard- standardization for precise weighing

Secondary standard- standardization according to the setting substance (solution of the setting substance).

SoHowsaltacidflying,standardsolutionherCancookonlybystandardizationByinstallationsubstance.

1 ) Preparationprimarystandard - solutioncarbonatesodium.

Calculate the amount of Na2CO3 required to prepare 100 cm3 of a 0.1 M solution, taking into account that the molar mass of the equivalent of sodium carbonate in the reaction with hydrochloric acid is 53 g/mol:

m (Na2CO3) = C (1/2Na2CO3) V (Na2CO3) M (1/2Na2CO3) = 0.1 mol/dm3 0.1 dm3 53 g/mol = 0.53 g.

Therefore, to prepare 100 cm3 of 0.1 M (1/2 Na2CO3) Na2CO3 solution, 0.53 g is required. Take a sample of sodium carbonate on a watch glass. It is difficult to weigh the accurately calculated mass, so they weigh it on technical scales required quantity salt, and then determine the mass of the sample on an analytical balance with an accuracy of 0.0002 g.

Place a dry funnel into a clean 100 cm3 volumetric flask and transfer a portion of sodium carbonate, thoroughly washing the watch glass and funnel with a small amount of distilled water from the wash. The volume of water in the flask should not be more than 2/3. Stir the contents of the flask until the salt is completely dissolved. Add distilled water to the flask to the mark. The addition of water is completed using a pipette, adding water drop by drop, holding the flask so that the mark is at eye level. Having prepared the solution, mix it thoroughly, closing the flask with a stopper. Calculate the concentration and titer of the prepared sodium carbonate solution using the formulas:

2 ) Preparation200 cm3approximately0,05 Msolutionsaltacids.

A solution of hydrochloric acid of a given concentration is prepared from more concentrated solution by dilution method. Calculate the amount of anhydrous acid required to prepare a 200 cm3 solution containing 0.05 mol HCl in 1 dm3. For further calculations, measure the density of a concentrated acid solution using a hydrometer. The hydrochloric acid solution is poured into a dry cylinder and

immerse the hydrometer in it. The reading on the hydrometer scale is carried out along the lower meniscus from top to bottom with an accuracy of 0.001 g/cm 3 . Using the table, find the percentage concentration of the acid and calculate the volume of the solution that contains the required amount of hydrochloric acid. ~ 150 cm 3 of distilled water is poured into a beaker with a volume of 250-300 cm 3. The calculated volume of the initial HCl solution is measured with a cylinder, poured into a beaker with water and added to the required volume, corresponding to 200 cm 3. The prepared solution is thoroughly mixed. The hydrochloric acid solution is ready for standardization.

3 ) StandardizationsolutionsaltacidsapproximatelynecessaryconcentrationsBycarbonatesodium.

Standardization of a hydrochloric acid solution is carried out using a primary standard of sodium carbonate, prepared by precise weighing. When titrating, use the indicator methyl orange.

The thoroughly washed burette is rinsed twice with small portions of the prepared hydrochloric acid solution. Using a funnel, fill the burette with acid until bottom edge The liquid meniscus was slightly above the zero mark. Then fill the burette spout with the acid solution, displacing air bubbles from the connecting hose. After removing the funnel, release the acid from the burette so that the lower edge of the meniscus is at the level of the zero division of the burette scale.

A clean 10.00 cm3 pipette is rinsed with sodium carbonate solution. Pipette 10.00 cm3 of Na2CO3 solution into the titration flask and add 1-2 drops of methyl orange indicator. A “witness” solution is prepared in another conical flask.

3 . Termscarrying outtitration.

State Pharmacopoeia X recommends titrating the sodium benzoate preparation in the presence of ether.

4 . Definitionultimatepointstitration.

The end point of the titration is determined visually by the change in color of the indicator present in the titrated solution.

In the chosen method, when the equivalence point is reached, the color of the mixed indicator (1 ml of methyl orange + 1 ml of methylene blue) changes color from green to lilac.

5 . Application.

Analysisdrug " Sodiumbenzoate" .

Methodology: about 1.6 g of the drug (exactly weighed) is transferred to a 25 ml volumetric flask, dissolved in freshly boiled and cooled water, and adjusted to the mark. Using a measuring pipette, take 10 ml of the resulting solution for titration, add 18 ml of ether, 2 drops of a mixed indicator (1 ml of methyl orange solution and 1 ml of methylene blue solution) and titrate with 0.5 N hydrochloric acid solution until a lilac color appears in the aqueous layer. At the end of the titration, the contents of the flask are shaken well. The content in the preparation must be at least 99.9% in terms of dry matter (weight loss upon drying is 2.5%).

M (C 7 H 5 NaO 2) = 144.11

III. Protocol for performing a titrimetric analysis of a sodium benzoate preparation using direct acidimetry with a solution of 0.05 N. hydrochloric acid in the presence of ether

Accurateweightweightspowderbenzoatesodium: m= 1.6003 g

Schemereactions:

M (C 7 H 5 NaO 2) = 144.11, f eq. =1

M eq. (C 7 H 5 NaO 2) = 144.11

Volumespenttitrant:

V 1 = 7.82 ml

V 2 = 7.80 ml

V 3 = 7.84 ml

V avg. = 7.82 ml

TitersolutionsaltacidsBybenzoatesodium:

= = = 0,0072

CalculationpercentagecontentbenzoatesodiumVdrug:

ы = = = 88.04%

WITHtaking into accountlossesweightatdrying:

88%*102,5% = 90,24%

BystandardmassivesharebenzoatesodiumVdrugshouldhesitateVwithin99,0% - 103, 0% .

Conclusion: in terms of the percentage of sodium benzoate, the analyzed drug does not meet the requirements of the State Pharmacopoeia of the Russian Federation.

Literature used

1. State Pharmacopoeia of the USSR. - 10th ed. - M.: Publishing house "Medicine", 1968.

2. Kharitonov Yu.Ya. Analytical chemistry. Analytics: in 2 books. - 2nd ed. - M.: graduate School, 2003.

3. Belikov V.G. Pharmaceutical chemistry. At 2 o'clock: Educational. manual - M.: MEDpress-inform, 2007 - 624 p.

4. Arzamastsev A.P. Pharmaceutical chemistry: Textbook. manual - M.: GEOTAR-MED, 2004 - 640 p.

5. Guide to laboratory classes in analytical chemistry. Qualitative analysis. Abdullina S.G., Shchukin V.A. - Kazan, 2007.

6. Encyclopedic Dictionary Brockhaus and Efron: In 86 volumes (82 volumes and 4 additional). - St. Petersburg, 1890-1907.

7. State pharmacopoeia Russian Federation/ Publishing house " Science Center examination of funds medical use", 2008. - 704 p.: ill.

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1. Russian name medicine.

Sodium benzoate

Sodium benzoic acid

Sodium benzoic acid

Sodium benzoate

2. Latin name medicine.

Natrium benzoicum

3. Chemical formula indicating molar mass

Molar mass 144,11

4. Appearance

White crystalline powder, odorless or with a very faint odor, sweetish-salty taste.

5. Physical and chemical properties

Density: 1.44 g/cm3

Solubility.

Easily soluble in water, difficultly soluble in alcohol.

Transparency and color of the solution.

A solution of 1 g of the drug in 10 ml of freshly boiled and cooled water should be transparent and colorless.

Alkalinity and acidity.

A few drops of phenolphthalein solution are added to the resulting solution; the solution should remain colorless. A pink color should appear from adding no more than 0.75 ml of 0.05 N. caustic soda solution.

0.15 g of the drug is dissolved in 14 ml of water, 1 ml of diluted nitric acid is added and filtered. 10 ml of the filtrate must pass the test for chlorides (no more than 0.02% in the drug).

1.5 g of the drug is dissolved in 25 ml of water, 5 ml of diluted hydrochloric acid is added and filtered. 10 ml of the solution must pass the test for sulfates (no more than 0.02% in the drug).

10 ml of the same filtrate must pass the test for heavy metals (no more than 0.001% in the preparation).

Weight loss during drying.

About 1.5 g of the drug (exactly weighed) is dried at 100-105 to constant weight. Weight loss should not exceed 3%.

Humidity: no more than 2%.

Note. Sodium benzoate for the preparation of injection solutions must additionally pass a test for iron: a solution of 0.4 g of the drug in 10 ml of water must pass the test for iron (no more than 0.0075% in the drug).

6. Methods of obtaining

Sodium benzoate is obtained by the reaction of benzoic acid with a solution of sodium hydroxide or sodium carbonate:

a) with sodium hydroxide:

sodium benzoate chemical analysis

b) with sodium carbonate:

2+ Na 2 CO 3 2 + H 2 O + CO 2

7. Qualitative analysis

The drug gives a characteristic reaction to benzoates and reaction B to sodium.

Qualitative reaction to benzoates:

To 2 ml of a neutral benzoate solution (0.01-0.02 g of benzoate ion) add 0.2 ml of ferric oxide chloride solution; a pinkish-yellow precipitate is formed.

6C 6 H 5 COONa + 2FeCl 3 + 10H 2 O (C 6 H 5 COO) 3 Fe Fe(OH) 3 7H 2 O + 6NaCl + 3C 6 H 5 COOH

Qualitative reaction to sodium ions:

a) Dry reaction. Sodium salt added to a colorless flame turns it yellow.

b) With zinc acetate: (a yellow crystalline precipitate forms)

Na + +Zn [ (UO 2) 3 (CH 3 COO) 8 ] +CH 3 COOH + 9H 2 O = NaZn [ (UO 2) 3 (CH 3 COO) 9 ] 9H 2 O + H +

c) With a solution of picric acid (a yellow crystalline precipitate forms)

C 6 H 2 (NO 2) 3 OH + Na + > C 6 H 2 (NO 2) 3 ONa + H +

Methodology for determining authenticity according to State Pharmacopoeia X:

0.25 g of the drug is dissolved in 5 ml of water, 1 ml of nitric acid is added, the separated white crystals are filtered off, washed with water and dried in a desiccator over sulfuric acid until a constant weight is achieved. The temperature of the resulting benzoic acid is 120-124.5°C.

Reaction scheme:

C 6 H 5 COONa + HNO 3 C 6 H 5 COOH + NaNO 3

8. Quantitative analysis

About 1.5 g of the drug (exactly weighed) is dissolved in 20 ml of water in a flask with a ground stopper with a capacity of 250 ml, add 45 ml of ether, 3-4 drops of a mixed indicator (1 ml of methyl orange solution and 1 ml of methylene blue solution) and titrate 0.5 n. with a solution of hydrochloric acid until a lilac color appears in the aqueous layer. At the end of the titration, the contents of the flask are shaken well.

1 ml 0.5 n. hydrochloric acid solution corresponds to 0.07205 g of sodium benzoate, which in terms of dry matter must be at least 99.0%.

9. Application

1. Drug: Sodium benzoate

Pharmacological group: secretolytics and stimulants of motor function of the respiratory tract.

As an expectorant - alone (per se) and as part of combined preparations. When taken orally, it increases the secretion of the mucous membrane of the respiratory tract.

2. Drug: Caffeine-sodium benzoate

Pharmacological group: respiratory stimulants, psychostimulants

Diseases accompanied by depression of the central nervous system, functions of the cardiovascular and respiratory systems (including drug poisoning, infectious diseases), cerebral vascular spasms (including migraine), decreased mental and physical performance, drowsiness, enuresis in children, breathing disorders (periodic breathing, idiopathic apnea) in newborns (including premature infants).

10. Storage conditions

In a well-closed container, in a dry place, protected from light.

8. Give examples of medicinal substances that, like hexamidine, can decompose with the release of formaldehyde. Write the equations for the corresponding reactions.

9. Which of the medicinal substances in this group can react to form an azo dye? Specify the conditions for this reaction and write its chemistry.

10. Give methods that allow you to open the benzoic acid residue in benzonal. Write the reaction equations.

11. Give possible methods for detecting organically bound fluorine in fluorouracil and fluorafur. Write the reaction equations.

12. Write structural formulas fluorouracil, fluorafur, cytarabine and azidothymidine. Indicate the relationship between their structure and pharmacological action.

13. Based on the chemical structure of medicinal substances of the pyrimidine group, justify possible methods for their quantitative determination.

14. Explain the possibility of using physicochemical methods (UV and IR spectroscopy, various types chromatography) in pharmaceutical analysis barbiturates, uracil and haxamidine derivatives.

16. Specify the storage conditions for barbiturates in accordance with their physicochemical properties and medical use

List of literature for preparation.

1. Belikov, chemistry: Proc. For universities. – Pyatigorsk, 2003. P. 284-292.


2. Pharmaceutical chemistry: Textbook. Manual / Ed. . – 2nd ed., rev. – M.: GOETAR-Media, 2005. P.249-293.

LESSON 5

Drug analysis,

purine derivatives.

Purpose of the lesson:

Study the properties, identification reactions and methods of quantitative determination of medicinal substances of the purine group

Tasks:

Answer questions from incoming inspection;

Study the properties of medicinal substances, purine groups;

Execute research work to identify substances of the purine group, conduct a pharmacopoeial analysis of the identified substance;

Conduct an analysis of the proposed dosage forms in accordance with the requirements of intrapharmacy control of drugs containing substances of dual and variable composition.

In the process of self-study and in class, the student must acquire the following knowledge and skills:

Know:

Reactions for identifying drugs of the purine group;

Reactions for quantitative determination of drugs, purine group;

Application of Tusl for the quantitative determination of substances of dual and variable composition;

Pharmacopoeial methods for analyzing purine group drugs

Be able to:

Identify medicinal substances, purine groups and conduct their pharmacopoeial analysis;

Conduct analysis of dosage forms containing substances of dual and variable composition;

Prepare reporting documentation.

Lesson assignment:

Conduct an analysis of dosage forms containing substances of dual and variable composition;

Conduct a pharmacopoeial analysis of the substance ( caffeine-sodium benzoate, aminophylline).

Prepare an analytical passport.

General theoretical principles on the analysis of LF of dual and variable composition.

The principle of calculating titers for substances of dual or variable composition when analyzing dosage forms.

1. According to the regulatory documentation, the compound for which the substance of dual or variable composition is standardized is established, and the content of this compound is determined in %.

2. In accordance with the quantitative determination method, the titer of the compound being determined is calculated.

3. Calculate the titer of a substance of dual or variable composition, taking into account the actual content of the analyte in it, according to the formula:

TV-va= Topred. connection∙100% / (actual content in the compound in%)

Calculation of titers of dual-composition drugs (caffeine-sodium benzoate, aminophylline and others) when analyzing their dosage forms during intrapharmacy control.

In express analysis, the determination is usually carried out on one of the components of the drug, and is calculated on the drug as a whole.

1. Caffeine is sodium benzoate.

Determination of sodium benzoate by acidimetry.

feq. sodium benzoate = 1 M = 144.11 g/mol.

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In order to calculate the titer of caffeine-sodium benzoate, it is necessary to know the percentage of sodium benzoate in the drug. According to the State Fund of X, the sodium benzoate content should be in the range of 58-62%. If the sodium benzoate content in the preparation is 60%, then

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In 100 g of caffeine - sodium benzoate - 40 g of caffeine

X - 0.004855 g

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In 100 g of aminophylline - 14 g of ethylenediamine

X - 0.003050 g

Ammonia" href="/text/category/ammiak/" rel="bookmark">ammonia; observe the effect of the reaction.

2. Reaction with Wagner's reagent. 0.01 g of the drug is dissolved when heated in 0.5-1.0 ml of water, add 1-2 drops of iodine solution 0.1 mol/l, 1-2 drops of diluted hydrochloric acid and observe the effect of the reaction.

3. Reaction with tannin. 0.03 g of the drug is dissolved in 2 ml of water, a 0.1% tannin solution is added dropwise and the effect of the reaction is observed.

4. Reaction with cobalt chloride. 0.1 g of the drug is shaken for 2-3 minutes with ml of 0.1 mol/l sodium hydroxide solution and filtered. Add 2 drops of 2% cobalt chloride solution to the filtrate and observe the effect of the reaction.

5. Reaction with silver nitrate. 0.05 g of the drug is dissolved in a mixture of 1 ml of water and 0.5 ml of ammonia solution, add 0.5 ml of silver nitrate solution, mix and observe the effect of the reaction.

Specific reactions for the authenticity of purine derivatives

Caffeine sodium benzoate.

0.01 - 0.02 g of the drug is dissolved in 1 ml of water, 1-2 drops of iron (III) chloride solution are added. A pinkish-yellow precipitate is formed (detection of bound benzoic acid).

The sodium cation is proven by microcrystalloscopic reaction with picric acid.

Eufillin. 0.02 g of the drug is dissolved in 10 drops of water, 1 drop of copper sulfate solution (II) is added, a violet color appears (detection of ethylenediamine).

Substance caffeine benzoate-sodium.

Description . White crystalline powder, odorless, slightly bitter taste.

Solubility . Easily soluble in water, difficultly soluble in alcohol.

Authenticity .

0.5 g of the drug is dissolved in 3 ml of water, adding 1 ml of sodium hydroxide solution, 10 ml of chloroform and shaken for 1-2 minutes. The chloroform solution is filtered through a filter with anhydrous sodium sulfate and the chloroform is evaporated in a water bath. The residue gives the authenticity reactions characteristic of caffeine.

The drug solution reacts to benzoates

Acidity and alkalinity: Add a few drops of phenolphthalein solution to a solution of 0.25 g of the drug in 5 ml of freshly boiled and cooled water. The solution should not be colored pink. A pink color should appear from adding no more than 0.15 ml of 0.05 N. sodium hydroxide solution.

Weight loss on drying. About 0.5 g (exactly weighed) is dried at 800C to constant weight. Weight loss during drying should not exceed 5%

Quantification.

Caffeine: About 0.3 g (exactly weighed) of the drug is dissolved in 30 ml of water in a 100 ml volumetric flask. 10 ml of diluted sulfuric acid, 50 ml of iodine solution (0.1 mol/l, UC ½ I2) are added to the solution, the volume of the solution 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 10-15 ml of the filtrate is discarded. Transfer 50 ml of the filtrate into a flask and the excess iodine is titrated with a solution of sodium thiosulfate (0.1 mol/l) until discolored (indicator - starch). At the same time, a control experiment is carried out.

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 the chemical structure and properties, suggest possible methods for quantitative analysis 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. 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 organic acid, characterized by displacement-precipitation reactions.

The inorganic components of the dosage form are NaBr and MgSO 4 - 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