Caffeine sodium benzoate gf. Purine alkaloids

Authenticity reactions to benzoate

Qualitative reaction to sodium cation

Sodium turns a colorless burner flame yellow.

Task #7

For the production of "Bitter tincture", the enterprise purchased a batch of medicinal plant products "Three-leaf Watch Sheet" with a weight of 2160 kg (net), packed in bales of fabric with a weight of 40 kg (net). There were traces of smudges on three bales. To confirm the quality of raw materials, samples were taken and analyzed.

· What normative documentation is guided by during the acceptance and testing of samples?

· Calculate the sample size.

· How are the masses of the average and analytical samples determined? What is the quartering method?

LEAVES OF THE THREE-LEAF WATCH - FOLIA MENYANTHIDIS TRIFOLIATAE

Three-leaf watch - Menyanthestrifoliata

Rotational family - Menyanthaceae

Conclusion on the quality of raw materials:

According to GF XI - numerical indicators for whole raw materials: the amount of flavonoids in terms of rutin is not less than 1%; humidity no more than 14%; total ash not more than 10%; yellowed, blackened and browned leaves no more than 5%.

When carrying out acceptance and testing of samples, OFS 420013-03 "Rules for the acceptance of medicinal plant materials and sampling methods" are guided, and sample analysis is carried out in accordance with the State Pharmacopoeia XI edition.

The sample size is calculated for undamaged products, and three bales with traces of smudges are opened and analyzed separately.

The sample size is calculated according to table No. 1.

2160 / 40 = 54 (bales)  the sample size is 10% of the lot transport units, i. 6 bales.

From each opened unit of product, 3 point samples of the same weight are taken, mixed and a combined sample is obtained, from which an average sample is taken by quartering according to Table No. 2 (400.0), which are packaged and sent to the center for drug control and certification , there it is divided by the quartering method into 3 analytical samples:

the first (weighing 200.0) determine the authenticity, fineness and content of impurities;

the second (weighing 25.0) determine the humidity;

according to the third (weighing 150.0), ash content and active substances are determined.

The State Pharmacopoeia requires determining the amount of flavonoids in shamrock leaves in terms of rutin (according to the State Pharmacopoeia XI edition, not less than 1%).

The Quality Control Department of a pharmaceutical enterprise for the manufacture of tablets received several series of Rutin substance for quality assessment. In one series, the readings of optical density in the determination of quercetin impurities exceeded the regulated norm.

· Justify the reasons for the change in the impurity content.

· Give the chemical formula of this substance, its Latin and rational names.

· List its physico-chemical properties and standard indicators due to these properties.

· Suggest methods for qualitative and quantitative determination of rutin, write reaction equations.

Rutinum - Rutin

3-rutinoside quercetin; 3-rhamnoglycosyl-3,5,7,3",4"-pentaoxyflavone

The composition of the routine contains chemical groups: According to the chemical structure, rutoside is a glycoside. The sugar part (disaccharide of rutinose) includes D-glucose and L-rhamnose.

1. phenolic hydroxyls.

Description. Greenish-yellow crystalline powder, odorless and tasteless. Solubility. Practically insoluble in water, slightly soluble in 95% alcohol, hardly soluble in boiling alcohol, practically insoluble in acid solutions, in ether,

Rutin's analysis. 1. The IR spectrum must completely match the spectrum of the standard. 2. UV spectrum of a 0.002% solution of the drug in absolute alcohol has a max at 259 and 362.5 nm. Due to the aromatic system of quercetin.

Chemical reactions: 1) hydrolysis of the glycosidic bond occurs, and then a color reaction with a solution of sodium hydroxide (yellow-orange color), the color is due to the transformation of the flavonoid into chalcone with the opening of the pyran ring.

2) The cyanine reaction occurs when rutin is exposed to magnesium powder and conc. hydrochloric acid in an alcoholic medium. based on the formation of colored pyrylium salts during hydrogen reduction of flavonoids, including rutin

3) the sugar part (glucose) ODA with react. Fehling after hydrolysis.

Quantitative determination: Method – UV spectrophotometry.

Determine the optical density of the solution on a spectrophotometer at wavelengths of 375 nm (D1) and 362.5 nm (D2) in a cuvette with a layer thickness of 1 cm. calculated by the formula:

where 325.5 is the specific absorption index E\% cm of pure rutin (anhydrous) in absolute alcohol at a wavelength of 362.5 nm; a - weight in grams. If the D1/D2 ratio exceeds 0.879, then the percentage of rutin (X) is calculated using the formula:

3. In a pharmacy:

· Justify the rules for the introduction of alcohol-containing drugs in the manufacture of liquid dosage forms for internal and external use.

In the manufacture of JLF, alcohol-containing LF are often introduced (tinctures, liquid extracts, elixirs, novogalenic (maximally purified preparations) alcohol solutions). It should be guided by the provision of the order of the Ministry of Health and social. Development of Russia No. 308 dated 10/21/97:

Alcoholic solutions are prepared by mass-volume method;

If a solution is prescribed in the prescription without indicating the concentration; provided for in the ND with several concentrations of the drug, a solution of low concentration should be dispensed (for example, a solution of boric acid 0.5%, 1%, 2%, 3%, 5% - dispense a 1% solution, iodine solution 1%, brilliant green 1 % etc.)

The rate of dispensing of alcohol of registration concentration in terms of mass is 50.0, in case of indication for a special purpose - no more than 100.0.

In complex mixtures, alcohol-containing liquids should be added in ascending order of alcohol strength to avoid the formation of a precipitate of active ingredient.

Alcohol in the manufacture of extemporaneous preparations is measured by volume, and taken into account by weight in terms of 95 - 96%.

Prescription form No. 148, alcohol is on the PKU.

4. Focus on organizational and economic aspects:

· What is the procedure for pricing, dispensing from a pharmacy and accounting for ethyl alcohol, alcohol-containing dosage forms and factory-made alcohol tinctures?

Gross formula

C 8 H 10 N 4 O 2

Pharmacological group of the substance Caffeine

Nosological classification (ICD-10)

CAS code

58-08-2

Characteristics of the substance Caffeine

Pharmacology

pharmachologic effect- analeptic, cardiotonic, psychostimulant.

It has a direct stimulating effect on the central nervous system: it 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 taking it, cheerfulness appears, fatigue and drowsiness are temporarily eliminated or reduced. Causes quickening 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). Expands bronchi, biliary tract, blood vessels of skeletal muscles, heart, kidneys, narrows - 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 the stomach 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. It inhibits cAMP phosphodiesterase to a greater extent (not only in the central nervous system, but also in the heart, smooth muscle organs, adipose tissue, 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). T 1/2 is about 5 hours, in some individuals - up to 10 hours. The main part is demethylated and oxidized. About 10% is excreted by the kidneys unchanged. 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 is largely dependent on the dose and type of the patient's nervous system. In small doses, the stimulating effect prevails, in large doses it is depressing. In older people, the effect on sleep is more pronounced: its onset slows down, total sleep time decreases, and the frequency of awakenings increases (possibly due to faster metabolism of catecholamines in the central nervous system). In premature infants, when periodic breathing is eliminated, caffeine reduces the partial pressure of carbon dioxide, the concentration of H + blood and at the same time increases the volume of ventilation without changing the heart rate.

The 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), spasms of cerebral vessels (including migraine), decreased mental and physical performance, drowsiness, enuresis in children, respiratory disorders (periodic breathing, idiopathic apnea) in newborns (including premature babies).

Contraindications

Severe arterial hypertension, organic diseases of the cardiovascular system (including atherosclerosis), irritability, glaucoma, sleep disturbances, old age.

Side effects of caffeine

Anxiety, agitation, insomnia, tachycardia, arrhythmias, increased blood pressure, nausea, vomiting. With prolonged 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 can lead to increased CNS inhibition with symptoms of fatigue, drowsiness and depression.

Interaction

Reduces the effect of sleeping pills and narcotic drugs, 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 150 ml cups of natural coffee) can cause anxiety, anxiety, tremor, headache, confusion, cardiac extrasystoles. In newborns (including premature babies), at a plasma concentration of 50 mg / ml, toxic effects are possible: anxiety, tachypnea, tachycardia, tremor, increased Moro reflex, and convulsions at higher concentrations.

sodium benzoate, sodium benzoate.

Chemical properties

Sodium Benzoate, what is it? The sodium salt of 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 the year 75 of the 19th century as a substitute. The tool has been used as a preservative since the beginning of the 20th century. In small doses, the substance is found in cranberries, apples, mustard and cinnamon.

The tool 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 a special paper that protects parts made of aluminum and galvanized.

The 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 foods, 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 a preservative, about its ability to cause severe oxidative stress, about mutagenic activity in relation to 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 to be relatively harmless. In rare cases, a chemical compound causes an exacerbation of symptoms and.

pharmachologic effect

Expectorant.

Pharmacodynamics and pharmacokinetics

What is Sodium Benzoate? The effect of sodium benzoate on the body

In sufficiently high concentrations, the drug has a depressing effect on the vital activity of molds and yeasts, inhibits the activity of enzymes responsible for the flow of ODS, which break down starch and fats. When taken orally, the substance stimulates the processes of mucus secretion, increases mucociliary clearance.

Indications for use

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

Contraindications

The agent is contraindicated for taking with the active component.

Side effects

Very rarely, Sodium Benzoate can cause allergic reactions, 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 course of treatment averages from 10 days to 2 weeks.

Overdose

Information about drug overdose is limited.

Interaction

There are no data on drug interactions of the drug.

Terms of sale

Non-prescription leave.

special instructions

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

During pregnancy and lactation

The substance can also be taken by lactating women according to the testimony of a doctor. If the potential benefit outweighs the risk to the health of the child.

Preparations containing (Analogues)

Substance in combination with , anise seed, extract thermopsis and licorice is included in . Also, the remedy is contained in the preparations: Amtersol , Dry cough medicine for children , Moneysoft , Tos-May , Extraterm .

Natrii benzoas

C 7 H 5 NaO 2 M. m. 144.11

Description. White crystalline or amorphous powder, odorless or with a very slight odor.

Solubility. Easily soluble in water, sparingly soluble in 90% alcohol, practically insoluble in ether and chloroform (SP XI, issue 1, p. 175).

Authenticity. The ultraviolet spectrum of a 0.001% aqueous solution of 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 give a characteristic reaction to benzoates (SP XI, issue 1, p. 159).

Solution transparency. A solution of 1 g of the drug in 10 ml of freshly boiled and cooled water must be transparent or be comparable with reference solution 1 (SP XI, issue 1, p. 198).

The 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 the addition of 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 alcohol 95% are added. The resulting solution must withstand the test for chlorides (not more than 0.02% in the preparation; GF 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 withstand the test for sulfates (not more than 0.02% in the preparation; GF XI, issue 1, p. 165).

Heavy metals. 0.5 g of the drug is dissolved in 5 ml of water, 5 ml of alcohol 95% are added. The resulting solution must withstand the test for heavy metals (not more than 0.001% in the preparation; GF XI, issue 1, p. 165).

Weight loss on drying. About 0.5 g of the drug (accurately weighed) is dried at a temperature of from 100 to 105°C to constant weight. The loss in mass should not exceed 2.0% (GF XI, issue 1, p. 176).

Quantitation. About 1.5 g of the drug (accurately weighed) is dissolved in 20 ml of water in a flask with a ground stopper, with a capacity of 250 ml, 45 ml of ether, 0.2 ml of an indicator are added and titrated with a 0.5 M solution of hydrochloric acid until a lilac color appears in water. layer. Shake the flask well at the end of the titration.

1 ml of a 0.5 M hydrochloric acid solution corresponds to 0.07205 g of C 7 H 5 NaO 2 . The drug contains at least 99.0% g of 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, dark place, at a temperature above + 25 0 С.

Control questions and situational tasks.

1. Explain from an electronic point of view the acidic properties of phenols.

2. What is the field of application in the pharmaceutical analysis of reactions of electrophilic substitution of phenols? Give examples.

3. One of the chemical properties of phenols is their good oxidizability followed by condensation of the initial and formed products. Give examples of reactions of this type with chloramine or bleach using phenol as an example, with Mark's reagent (formaldehyde with concentrated sulfuric acid) using resorcinol as an example.

4. Give the reaction equations for the combination of phenols with a 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 be brominated and nitrated is used. What products are obtained from this? How can these reactions be used to authenticate 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 the chemical and trivial names, as well as the reaction in which it acts as a reagent.

7. One of the common identification reactions for phenolic hydroxyl is the reaction with ferric chloride. Name the type of reaction. Which of the following substances do not give this reaction: phenol, menthol, resorcinol, thymol.

8. GF X for testing the authenticity of resorcinol recommends the reaction of the formation of fluorescein. Write the reaction equation, name its type and stages.

9. Justify the iodine- and iodine-chlormetric methods for the analysis of 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 of aromatic acids and their salts.

12. Methods for obtaining aromatic acids and their derivatives.

13. General and private methods for identifying drugs in this group.

14. General and private 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 the equations, derive the equivalence factor.

17. Quantitative analysis of sodium benzoate according to the pharmacopoeial method is carried out by the acidimetric displacement method. Calculate the titer if hydrochloric acid solution (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, UCH 1/6 KBrO 3) was used to titrate a sample of 0.1501 g.

19. Calculate the mass of the powder of crushed vikasol tablets so that 22.5 ml of a solution of cerium (IV) sulfate (0.1 mol / l, UCH 1/2 Ce (SO 4) 2) is consumed for titration according to the GF method. The average tablet weight is 0.1014 g.

20. What weighed amount of resorcinol should be taken so that when determining by the iodine chlorometric method, 10 ml of sodium thiosulfate (0.1 mol/l) is used for back titration of the released iodine, the volume of iodine monochloride is 30 ml (0.1 mol/l, UCH ½ ICl) .

List of literature for preparation.

1. Belikov, V.G. Pharmaceutical chemistry: Proc. For universities. - Pyatigorsk, 2003. S. 258-266.

2. Pharmaceutical chemistry: Proc. Allowance / Ed. A.P. Arzamastsev. - 2nd ed., Rev. – M.: GOETAR-Media, 2005.

3. Chemical analysis of medicinal substances by functional groups. Teaching aid for students of the Faculty of Pharmacy. - Nizhny Novgorod: Publishing House of the Nizhny Novgorod State Medical Academy, 2003.

4. Organic drugs. aromatic compounds. Brief summary of lectures. - Nizhny Novgorod: Publishing House of the Nizhny Novgorod Medical Academy, 2004.

1. For analytical control of the substance of caffeine-sodium benzoate:

Give the chemical formula and rational name of caffeine-sodium benzoate. Substantiate its physico-chemical properties and suggest their use in the analysis of the quality of medicines.

· In accordance with the chemical structure and properties, suggest possible methods for the 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 an odorless white powder, slightly bitter in 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 fused heterocyclic system consisting of pyrimidine and imidazole cycles. It is a tertiary base, enters into oxidation and precipitation reactions.

Sodium benzoate is a salt formed by a strong base and a weak organic acid, precipitation displacement reactions are characteristic.

The inorganic components of the drug 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, showing reducing 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 derivatives of alloxan idialuric acid, the interaction of which forms alloxanthin, which forms the ammonium salt of tetramethylpurpuric acid in an ammonia medium.

This reaction is used to analyze the substance (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 reaction of complexation 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