Quantitative chemical analysis of a substance. Sodium benzoate. Caffeine sodium benzoate Quantitative determination of sodium benzoate gf

Authenticity.

Caffeine sodium benzoate

Coffeinum natrio-benzoicum

Receipt. The interaction of aqueous solutions of sodium benzoate and caffeine, the resulting solution is evaporated until a dry powder is formed.

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 - sodium bromide and caffeine-sodium benzoate solution; 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 benzoate, sodium benzoate.

Chemical properties

Sodium Benzoate, what is it? Sodium benzoic acid, a widely used preservative. It is a white fine powder, odorless or with a subtle odor benzaldehyde . Chemical formula: C6H5CO2Na. According to the pharmacopoeia, the molecular weight of the compound = 144.1 grams per mole. The substance was discovered in 75 of the 19th century as a substitute. The product has been used as a preservative since the beginning of the 20th century. The substance is found in small doses in cranberries, apples, mustard and cinnamon.

The product is used:

• as a dietary supplement E102,E110, E124, E104, E122 And E129;
• as a preservative in the pharmaceutical and cosmetic industries;
• in medicine, as an expectorant;
• in pyrotechnics and aviation to create special paper that protects aluminum and galvanized parts.

Harm of Sodium Benzoate

At the moment, the question of whether this component is harmful remains open. Since lactic acid, dyes and stabilizers are often present in various food products, potassium sorbate and Sodium Benzoate. The substance is approved for use in the CIS countries and Europe. It is added to mayonnaise, fish products, ketchup and margarine, sweet carbonated drinks, jams and berry products. However, there are a number of scientific works that talk about the dangers of the preservative, its ability to cause severe oxidative stress, and its mutagenic activity towards mitochondrial DNA. Molecular biologist Peter W. Piper believes that the substance can cause various neurodegenerative diseases and. According to WHO recommendations, the substance is considered relatively harmless. In rare cases, the chemical compound causes an exacerbation of symptoms and.

pharmachologic effect

Expectorant.

Pharmacodynamics and pharmacokinetics

What is Sodium Benzoate? Effect of sodium benzoate on the body

In sufficiently high concentrations, the drug has an inhibitory effect on the vital activity of molds and yeasts, suppresses the activity of enzymes responsible for the occurrence of ODS, breaking down starch and fats. When taken orally, the substance stimulates the processes of mucus secretion and increases mucociliary clearance.

Indications for use

The drug is prescribed for the complex treatment of inflammatory diseases of the respiratory tract, which are accompanied by, tracheitis , .

Contraindications

The drug is contraindicated for use with the active ingredient.

Side effects

Very rarely, Sodium Benzoate can cause allergic reactions and skin rashes.

Instructions for use (Method and dosage)

Preparations with the addition of this substance are prescribed orally.

Depending on the age and type of cough, different dosages and dosage forms are used. The average course of treatment ranges from 10 days to 2 weeks.

Overdose

Information about drug overdose is limited.

Interaction

There is no data on drug interactions.

Terms of sale

Over-the-counter release.

special instructions

Sodium benzoate should be used in accordance with the recommendations described in the instructions for a particular drug. Do not take after expiration date.

During pregnancy and lactation

The substance can also be taken by breastfeeding women as directed by a doctor. If the potential benefit outweighs the risk to the child's health.

Drugs containing (Analogs)

Substance in combination with anise seeds, extract thermopsis And licorice is included in the composition. The drug is also contained in the following preparations: Amtersol , Dry cough syrup for children , Manisoft , Tos-Mai , Extratherm .

Contains no less than 38.0% and no more than 42.0% caffeine and no less than 58.0% and no more than 62.0% sodium benzoate in terms of dry matter.

Description. White crystalline powder. Hygroscopic.

Solubility. Easily soluble in water, soluble in glacial acetic acid, moderately soluble in 95% alcohol.

Authenticity. 1. IR spectrum. Infrared spectrum of the substance residue obtained in the “Quantitative Determination” test. Caffeine”, removed in a disk with potassium bromide, in the region from 4000 to 400 cm -1, according to the position of the absorption bands, should correspond to the spectrum of the standard sample of caffeine.

2. Qualitative reaction. 0.5 g of the substance is dissolved in 3 ml of water, add 1 ml of 10% sodium hydroxide solution, 10 ml of chloroform and shake 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 reactions of authenticity indicated in the article “Caffeine Anhydrous”, and after drying at 80° to constant weight has a melting point of 234 - 237°.

3. Qualitative reaction. A 1:100 solution of the substance gives a characteristic reaction to benzoates.

4. Qualitative reaction. The substance gives a characteristic reaction B to sodium.

*Transparency of the solution. A solution of 0.5 g of the substance in 10 ml of water should be clear and should not become cloudy or precipitate when heated in a closed test tube in a boiling water bath for 30 minutes. (OFS “Transparency and degree of turbidity of liquids”).

*Color of the solution. The solution obtained in the “Transparency of solution” test must be colorless (General Pharmacopoeia Monograph “Degree of color of liquids”, method 2).

Acidity or alkalinity. 0.25 g of the drug is dissolved in 5 ml of freshly boiled and cooled water and 0.1 ml of 1% phenolphthalein solution is added. The solution should not turn pink. A pink color should appear from the addition of no more than 0.15 ml of 0.05 M sodium hydroxide solution.

Weight loss on drying. No more than 5.0% (General Pharmacopoeia Monograph “Weight loss on drying”, method 1). About 0.5 g (exactly weighed) of the substance is dried at a temperature of 80 ± 2 ºС.

Easily charred substances. 0.3 g of the substance is dissolved in 3 ml of concentrated sulfuric acid. The color of the solution should not be more intense than standard B 5 (General Pharmacopoeia Monograph “Color Degree of Liquids”, method 2). For a substance intended for the production of medicinal products for parenteral use, this solution must be colorless.

Sulfates. No more than 0.02% (OFS “Sulfates”, method 1). 0.5 g of the substance is dissolved in 5 ml of water, 5 ml of 95% alcohol is added.

Chlorides. No more than 0.02% (ODS “Chlorides”). 0.1 g of the substance is dissolved in 5 ml of water, 5 ml of 95% alcohol is added.

Heavy metals. Not more than 0.001% (OFS “Heavy metals”). 1.0 g of the drug is dissolved in 10 ml of water.

Residual organic solvents. In accordance with the General Pharmacopoeia Monograph “Residual Organic Solvents”.

*Pyrogenicity. The substance must be pyrogen-free (ODS “Pyrogenicity”). Test dose: 10 mg of substance in 1 ml of 0.9% sodium chloride solution per 1 kg of rabbit weight.

Microbiological purity. In accordance with the General Pharmacopoeia Monograph “Microbiological purity”.

Quantitation. 1. Sodium benzoate. About 0.3 g (exactly weighed) of the substance, previously dried to a constant weight, is dissolved in 2 ml of chloroform, 40 ml of acetic anhydride is added and titrated with a 0.1 M solution of perchloric acid in methanol to the first equivalence point, determined potentiometrically (OPS “Potentiometric titration").

At the same time, a control experiment is carried out.

1 ml of 0.1 M solution of perchloric acid in methanol corresponds to 14.41 mg of sodium benzoate C 8 H 10 N 4 O 2.

2. Caffeine. Titration continues from the first to the second equivalence point, determined potentiometrically (general pharmaceutical standard “Potentometric titration”).

Gross formula

Pharmacological group of the substance Caffeine

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Caffeine

Pharmacology

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, bile ducts, blood vessels of skeletal muscles, heart, kidneys, narrows the abdominal organs (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, and skeletal muscles). Stabilizes transmission in 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 of cortical functions) and medulla oblongata (excitation of the respiratory center), noradrenergic synapses (increased 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) it is eliminated more slowly (T 1/2 - from 80 to 26.3 hours, respectively).

The effect on higher nervous activity largely depends on the dose and type of the patient’s nervous system. 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 babies, 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, functions of the cardiovascular and respiratory systems (including drug poisoning, infectious diseases), cerebral vascular spasms (including migraine), decreased mental and physical performance, drowsiness, enuresis children, breathing disorders (periodic breathing, idiopathic apnea) in newborns (including premature infants).

Contraindications

Severe arterial hypertension, organic diseases of the 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. With long-term use, slight addiction is possible (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 other non-narcotic analgesics. Improves the absorption of ergotamine in the gastrointestinal tract.

Overdose

When abused, caffeine (more than 300 mg per day, i.e. four cups of natural coffee, 150 ml each) can cause anxiety, restlessness, tremors, headache, confusion, and 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.

172. Coffeenum

1,3,7-Trimethylxanthine

C 8 H 10 N 4 0 2 * H 2 0 M.v. 212.21

M.v. 194.19 (anhydrous)

Description. White silky needle-shaped crystals or white crystalline powder, odorless, bitter taste. It evaporates in air and sublimes when heated.

Solubility. Slowly soluble in water (1:60), easily soluble in hot water and chloroform, slightly soluble in alcohol, very slightly soluble in ether.

Authenticity. 0.01 G The drug is placed in a porcelain cup, 10 drops of diluted hydrochloric acid, 10 drops of perhydrol are added and evaporated to dryness in a water bath. The residue is moistened with 1-2 drops of ammonia solution; a purple-red color appears.

0,01 G the drug is dissolved in 10 ml water. K 5 ml the resulting solution is added dropwise with a 0.1% tannin solution; a white precipitate is formed, soluble in excess of the reagent.

0,05 G the drug is dissolved in 5 ml hot water, cool, add 10 drops of 0.1 N. iodine solution; There should be no sediment or turbidity. When adding a few drops of diluted hydrochloric acid, a brown precipitate is formed, soluble in excess alkali.

Melting point 234-237° (after drying at 80° to constant weight).

Acidity or alkalinity. 0.2 G the drug is dissolved in 10 ml freshly boiled hot water. When adding 5 drops of thymolphthalein solution to a cooled solution, no blue color should appear. The latter should appear when adding no more than 0.1 ml 0.05 n. caustic soda solution.

Foreign alkaloids. 10 ml solution of the drug (1: 100) should not produce cloudiness after adding a few drops of Mayer's reagent.

Organic impurities. 0.3 G drugs must dissolve in 3 ml concentrated sulfuric acid, as well as 3 ml concentrated nitric acid to form clear, colorless solutions.

Chlorides. 0.5 G the drug is shaken with 2 ml hot water, dilute with water to 25 ml and filtered through a filter previously washed with hot water. 10 ml This filtrate must pass the chloride test (not more than 0.01% in the preparation).

Sulfates. 10 ml the same filtrate must pass the test for sulfates (not more than 0.05% in the preparation).

Weight loss during drying. About 0.5 G The drug (accurately weighed) is dried at 80° to constant weight. Weight loss should not exceed 8.5% for caffeine monohydrate and 0.5% for caffeine anhydrous.

Sulfated ash and heavy metals. Sulfated ash from 0.5 G the preparation should not exceed 0.1% and must pass the test for heavy metals (no more than 0.001% in the preparation).

Quantitation. About 0.15 g of the drug, previously dried at 80° to constant weight (exactly weighed), is dissolved in 10 ml acetic anhydride when heated in a water bath, add 20 ml benzene, 5 drops crystal violet and titrate with 0.1 N. perchloric acid solution until a yellow color is obtained.

At the same time, a control experiment is carried out.

1 ml 0.1 n. perchloric acid solution corresponds to 0.01942 G C 8 H 10 N 4 O 2, which must be at least 99.0% in the dried preparation.

Storage. List B. In a well-closed container.

Highest single oral dose 0.3 G.

Highest daily oral dose 1.0 G.