In the nitrofural molecule, the nitrogen of the imine group has basic properties and participates in complexation reactions with cations heavy metals.
As a result of a shift in electron density to carbonyl oxygen, nitrofural exhibits the properties of a weak NH acid.
Nitrofural is characterized by prototropic tautometry:
Quality control
Determination of authenticity. The authenticity of furatsilin is determined by spectrometric methods.
Identification by IR spectroscopy consists of comparing the resulting spectrum with the spectrum of a working standard sample of furatsilin.
The absorption of a solution of furatsilin, obtained by dissolving a sample of the substance in DMF, has two maxima: at 260 and 375 nm. The ratio of absorbance measured at 375 nm to absorbance measured at 260 nm is between 1.15 and 1.30.
Determining authenticity by the ratio of solution absorptions at two wavelengths A 375 / A 260 allows testing without a standard sample.
A standard sample of nitrofural is necessary when determining authenticity using chromatography in a thin layer of silica gel. 10 mg of nitrofural and 10 mg of its standard sample are dissolved in 10 ml of methanol. A mixture of methanol and nitromethane (10:90 V/V) is used as the mobile phase, and a solution of phenylhydrazine hydrochloride is used as the developer. The main spot of the analyte in size, position and color intensity must coincide with the results of TLC determination for the nitrofural standard.
The authenticity of nitrofural is also determined chemical method. To do this, about 1 mg of the substance is dissolved in 1 ml of dimethylformamide. Add to the resulting solution alcohol solution KOH, a red-violet color appears. It can be assumed that, like aliphatic nitro compounds, potassium nitronate is formed in solution:
The interaction of furan derivatives with concentrated alkalis leads to the rupture of the furan ring and side chain with the formation various products decomposition: formaldehyde with a characteristic pungent odor and ammonia, which turns wet litmus paper blue.
The reaction of hydrolytic cleavage of furatsilin in alkaline environment:
Unofficial reaction: the formation of crystals of 2,4dinitrophenylhydrazone-5-nitrofurfural (mp 273 °C) as a result of boiling a solution of the drug in a DMF solution with a saturated solution of 2,4-dinitrophenylhydrazine and a 2 mol/l solution of hydrochloric acid. 1st stage:
Nitrofural is characterized by complexation reactions. In a solution of the substance in dimethylformamide, with the addition of pyridine and a solution of copper salt CuSO 4, a colored coordination compound is formed:
Purity tests. Monitor the pH value of the furatsilin solution. To do this, 1.0 g of the substance is dissolved in 100 ml of water (freed from carbon dioxide), shaken and filtered. Filtrate pH 5.0-7.0.
Impurities of related substances are controlled by liquid chromatography. These include, for example:
Sulfated ash - no more than 0.1% per 1.0 g.
When testing for purity, the loss in mass upon drying is determined. The mass of the substance should not decrease by more than 0.5% for a 1 g sample when dried in an oven at 105 °C.
quantitation. Quantitative determination of nitrofural is carried out in a place protected from bright light. Dissolve 60 mg of the substance in dimethylformamide and dilute the resulting solution with water to 500 ml. A 5 ml aliquot is diluted to 100 ml with water. A solution of a standard sample of nitrofural is prepared in a similar way. Electronic spectra of both solutions are taken and absorption is measured at a wavelength of 375 nm. The nitrofural content in the substance is calculated using the formula:
Where Cx And Cst- concentrations, Ax And Ast- light absorption of solutions of the analyzed substance and standard sample.
Introduction
For 60 years, in medical practice and veterinary medicine, drugs derived from 5-nitrofuran have been used to treat bacterial and some protozoal infections. The antimicrobial activity of this class of chemical compounds was first established in 1944 by M. Dodd, W. Stillman and immediately attracted the attention of physicians. Studies have shown that among numerous furan derivatives that have been studied since the end of the 18th century, only compounds containing a nitro group (NO2) strictly in the position of the 5th furan ring are characterized by antimicrobial properties.
A number of different 5-nitrofuran derivatives were proposed for use in medical practice in the 50–60s of the twentieth century. Then, due to the introduction into clinical practice of a large number of highly effective chemotherapeutic drugs in other classes of chemical substances, which exceeded the degree of activity of nitrofurans and had a number of advantages in pharmacokinetic and toxicological characteristics, interest in the drugs in this group decreased. Nevertheless, nitrofurans are still used in medical practice. The very first nitrofurans are still of practical interest - nitrofurantoin (furadonin), furazolidone, furazidin (furagin) and nitrofural (furatsilin).
The object of study for the coursework is nitrofural (furatsilin).
The purpose of my course work:
Carry out a qualitative determination of the substance (furatsilin) using known pharmaceutical methods and propose new ones;
Carry out quantitative determination and determine the simplest and most optimal method.
Furacilin (Furacilinum)
5-nitrofurfural semicarbazone
5-nitrofurfuryledene semicarbazide
Synonyms:
- Amifur;
- Vabrocid;
- Vatrocin;
- Vitrocin;
- Nitrofurazon;
- Nitrofural;
- Nitrofuran;
- Otofural;
- Flavazone;
- Furazem;
- Furaldon;
- Furacin;
- Chemofuran.
Physical properties:
Furacilin (C 6 H 6 O 4 N 4) is a yellow or greenish-yellow crystalline powder, odorless, bitter in taste. Melts at a temperature of 227-232°C with decomposition. Very slightly soluble in water (1:4200), slightly soluble in 95% alcohol, practically insoluble in ether, soluble in alkalis.
Aqueous solutions lose their antimicrobial activity during long-term storage.
Refers to derivatives of 5-nitrofuran.
Pharmacological action:
Antimicrobial agent, nitrofuran derivative. Active against gram-positive bacteria: Staphylococcus spp., Streptococcus spp., Bacillus anthracis; gram-negative bacteria: Escherichia coli, Shigella spp., Salmonella spp. (including Salmonella paratyphi).
Receipt:
The starting product for the synthesis of all drugs of the nitrofuran series is a very accessible substance - furfural, obtained from waste of various agricultural products (corn cobs, sunflower husks, etc.).
Furfural is nitrated by nitric acid in the presence of acetic anhydride, which reacts with the aldehyde group of furfural, protecting it from oxidation by nitric acid. Received
5-nitrofurfural diacetate is hydrolyzed with sulfuric acid to produce 5-nitrofurfural.
Indications for use of the drug:
- purulent wounds;
- bedsores;
- burns II–III degree;
- to prepare the granulating surface for skin grafting;
- blepharitis;
- conjunctivitis;
- external boils ear canal;
- osteomyelitis;
- empyema of the paranasal sinuses and pleura (washing the cavities);
- sharp external and otitis media;
- stomatitis;
- gingivitis;
- minor damage skin (including abrasions, scratches, cracks, cuts).
Composition and release form:
- Furacilin powder in glass bottles of 10 g;
- Tablets for oral administration containing 0.1 g of furatsilin, in packages of 12, 24 and 30 tablets;
- Combined tablets for external use with the following composition: furatsilin - 0.02 g, sodium chloride - 0.8 g; in packs of 10, 20 and 25 tablets;
- 0.02% solution of furatsilin (1:5000) for external use in 200 ml bottles;
- 0.2% furacilin ointment (1:500) in tubes of 25 g;
- Furacilin paste composition: furatsilin - 0.2 g, kaolin - 100.0 g, gelatin - 10.0 g, talc - 100.0 g, glycerin - 40.0 g, perfume oil or vaseline oil - 75.0 g, sodium carboxymethylcellulose - 20.0 g, salicylic acid - 5.0 g, boric acid - 3.0 g, ethyl alcohol - 12.0 g, disilled water - 634 ml, fragrance (benzaldehyde) - 1.0 g.
Storage conditions:
- Store in a dry place, protected from light, at a temperature not exceeding 25°C;
- Shelf life: 5 years;
- Keep out of the reach of children;
- Do not use after expiration date.
Identification
Some authors recommend using a reaction with dimethylformamide (DMF) to identify furatsilin. The resulting product is yellow in color. They also react with heavy metals. So, when adding a solution of copper (II) sulfate, furatsilin gives a dark red precipitate. It is known that furatsilin undergoes hydrolytic cleavage. As a result, the furan cycle breaks and furacilin can be detected by the resulting decomposition product - ammonia:
Furacilin with a zinc granule in an alkaline solution of β-naphthol changes color to brown-brown. A reaction has been described for furatsilin, which distinguishes it from all other drugs of the nitrofuran series - this is a reaction with resorcinol in a hydrochloric acid environment. Fluorescence is observed, which increases with the addition of isoamyl alcohol.
quantitation
A weighed portion of the drug is dissolved in water when heated in a water bath. For better solubility, sodium chloride is added. Then an excess of titrated iodine solution and 0.1 ml of sodium hydroxide solution are added to a certain amount of this solution. oxidative decomposition of the hydrazine group to nitrogen occurs.
In an alkaline environment, iodine can react with alkali and produce hypoiodides.
When sulfuric acid is added, iodine is released, which is titrated with sodium thiosulfate.
Indicator – starch:
2. Also, for the quantitative determination of furatsilin, the UV spectra of its 0.0006% solutions in a mixture of dimethylformamide with water (1:50) are used. The absorption maxima of such a solution in the region of 245-250 nm are at 260 and 375 nm, and the minima are at 306 nm. The maxima of the second absorption band (365-375 nm) are more specific, because are due to the presence of different electron-donating groups at position 2 of the furan ring. 3. Spectrophotometry (at a wavelength of 375 nm)
experimental part
Qualitative analysis.
1. Reaction with sodium hydroxide.
About 0.005 g of the substance is dissolved in a mixture of 0.5 ml of water and 0.5 ml of 10% sodium hydroxide solution, the color change of the solution is observed - orange-red.
2. Reaction with DMF.
0.005-0.01 g of the substance is dissolved in 3 ml of dimethylformamide. 1-2 drops of a 1 M aqueous-alcohol solution of potassium hydroxide are added to the resulting solution, and a color change is observed - yellow color.
3. Reaction with heavy metals.
To 0.002 - 0.005 g of the substance add 2 drops of 96% alcohol, 10% copper (II) sulfate solution and 10% sodium hydroxide solution, observe a color change - a dark red precipitate.
4. A solution of the drug in a 10% sodium hydroxide solution is heated to a boil, and wet red litmus paper is added to the vapor. The release of ammonium hydroxide is detected by the blueness of red litmus paper and by the smell.
5. Dissolve 0.01 g of the substance in 5 ml of water and heat to a boil. Cool and add zinc granule and 1 ml of hydrochloric acid. Leave for 20 minutes. After adding sodium nitrite to an alkaline solution of beta-naphthol, a color change is observed - brownish-brown.
6. A reaction (non-pharmacopoeial) has been described for furatsilin, which distinguishes it from all other drugs of the nitrofuran series - this is a reaction with resorcinol in a hydrochloric acid environment. When the reaction mixture is heated and subsequently made alkaline, fluorescence is observed, which increases with the addition of isoamyl alcohol
7. Hydrolytic cleavage.
0.01 - 0.02 g of the substance is dissolved in 10 ml of sodium hydroxide and heated. The furan cycle breaks with the formation of ammonia, which is detected by changes in red litmus paper, hydrazine and sodium carbonate.
Quantitation.
Yodimetric determination.
About 0.02 g of the drug (exactly weighed) is placed in a 100 ml volumetric flask, 1 g of sodium chloride, 70 ml of water are added and dissolved by heating to 70-80 ° C in a water bath. The cooled solution is brought to the mark with water and mixed. 5 ml of iodine solution is placed in a 50 ml flask with a ground-in stopper, 0.1 ml (2 drops) of sodium hydroxide solution is added and 5 ml of prepared furatsilin is added. Leave for 1-2 minutes in a dark place. Then I add 2 ml of diluted sulfuric acid to the solution and the released iodine is titrated with sodium thiosulfate solution. The indicator is starch. At the same time, a control experiment is carried out (95 ml), 01 M iodine solution + 0.1 ml sodium hydroxide solution + 2 ml diluted sulfuric acid).
1 ml of 0.01 N iodine solution corresponds to 0.0004954 g of furatsilin, of which the preparation must contain at least 97.5%.
where, a is the weight of furatsilin, g;
Va – aliquot volume, ml;
K – correction factor of 0.01 M sodium thiosulfate solution;
T – titer for the analyte, g/ml.
We carry out 6 repeated experiments.
M.m. (furacilin) = 198.14 g/mmol;
where, a is the weight of furatsilin, g;
K – correction factor of 0.01 M sodium thiosulfate solution;
Va – aliquot volume, ml.
Vt = = = 3.6 ml;
V experiment = 0.7 ml;
g (g) = = = 0.01
Vt = 3.5 ml;
V op = 0.9 ml;
Vt = 4.3 ml;
Vop = 0.6 ml;
V op = 0.7 ml;
Vt = 3.7 ml;
Vop = 0.7 ml;
Vt = 4.2 ml;
Vop = 0.5 ml;
Statistical processing of quantification data using the iodymetry method
0,02% - 200,0
Characteristics of the finished product
A solution of furatsilin 0.02% with sodium chloride 0.9% is sterile.
Compound
Furacilina 0.2 g
Sodium chloride 0.2 g
Water for injections up to 1 l
Transparent yellow liquid, pH=5.2-6.8, odorless.
The drug must meet the requirements specified in Art. in terms of sterility and the absence of mechanical impurities. GF XI, issue. 2, p. 140.
The drug is produced in 200 and 400 ml bottles for blood and blood substitutes, sealed with rubber stoppers 25P, IR-21 and aluminum caps.
The drug is stored at room temperature (not higher than 25 o C) in a place protected from light. Shelf life 1 month.
Used during neurosurgical operations, for treating wounds and cavities after operations, during purulent processes, instillations Bladder and etc.
Authenticity
1. Add 2-3 drops of sodium hydroxide to 0.5 ml of solution. A bright red color appears.
5-nitrofurfural semicarbazone
2. To 0.5 ml of solution add 2-3 drops of diluted nitric acid and silver nitrate solution. A white cheesy precipitate is formed, soluble in ammonia solution (chlorides).
3. A graphite stick is moistened with the solution and placed into a colorless flame. Flame coloration is observed yellow(sodium).
quantitation
Method: IODOMETRY, in alkaline medium, back titration, E= 1 / 4 M.m.
Place 2 ml of 0.01 N iodine solution in a flask with a capacity of 50 ml, with a ground-in stopper, and add 2 drops of sodium hydroxide solution (until the iodine discolors), 2 ml (0.02%) or 5 ml (0.01%) of the test substance solution, close with a stopper, mix and leave for 2 minutes in a dark place.
Then 2 ml of dilute sulfuric acid is added and the released iodine is titrated from a microburette with 0.01 N sodium thiosulfate (starch as indicator). At the same time, a control experiment is carried out. 1 ml of 0.01 N iodine solution corresponds to 0.0004954 g of furatsilin.
pH determination
Determination is carried out using a pH meter or RIFAN indicator paper.
Protocol No. 3
Aseptic block. Organization of work under aseptic conditions.
Asepsis includes a series of sequential measures that complement each other, and an error made in one link of this series nullifies all the work carried out and subsequent work.
1. Pre-aseptic (gateway) - designed to prepare personnel for work.
2. Aseptic - intended for the preparation of dosage forms.
3. Hardware - it contains autoclaves, sterilizers, and devices that allow the production of water for injection.
Premises requirements. The production of drugs under aseptic conditions is carried out in “clean” rooms in which air purity is standardized based on the content of microbial and mechanical particles.
The aseptic unit is usually located away from sources of contamination by microorganisms (patient service area, washing room, packaging room, sanitary unit).
In rooms for the preparation of medicines under aseptic conditions, the walls must be painted oil paint or lined with light-colored tiles, and there should be no protrusions, cornices, or cracks. Ceilings are painted with adhesive or water-based paint. The floors are covered with linoleum or relin with mandatory welding of the seams. Doors and windows must fit tightly and have no gaps.
The aseptic unit is equipped with supply and exhaust ventilation with a predominance of air flow over the hood. To reduce microbial contamination, it is recommended to install air purifiers that provide effective cleaning air filtration through ultrafine fiber filters and ultraviolet irradiation.
To disinfect the air in the aseptic unit, unshielded bactericidal irradiators are installed: wall-mounted BN-150), ceiling-mounted (OBP-300), mobile lighthouse type BPE-450); bactericidal lamps BUV-25, BUV-30, BUV-60 at a power rate of 2-2.5 W per 1 m 3 of room volume, which are turned on for 1-2 hours before starting work in the absence of people. The switch: these irradiators must be located in front of the entrance to the room, interlocked with a light sign “Do not enter, the bactericidal irradiator is on.” Entry into a room where an unshielded bactericidal lamp is turned on is permitted only after it is turned off; a long stay in the specified room is only 15 minutes after the unshielded bactericidal lamp is turned off.
In the presence of personnel, shielded bactericidal irradiators can be used, which are installed at a height of 1.8-2 m, at the rate of 1 W per 1 m 3 of the room, provided that directed radiation to people in the room is excluded.
Since ultraviolet irradiators produce toxic products in the air (ozone and nitrogen oxides), ventilation must be turned on when operating.
All equipment and furniture brought into the aseptic unit are pre-treated with wipes moistened with a disinfectant solution (chloramine B solution 1%, chloramine B solution 0.75% with 0.5% detergent, 3% hydrogen peroxide solution with 0.5% detergent). Storing unused equipment in an aseptic unit is strictly prohibited. The aseptic unit is cleaned at least once per shift using disinfectants.
Held once a week spring-cleaning aseptic block. At the same time, if possible, the premises are cleared of equipment, walls, doors, and floors are washed and disinfected. After disinfection, irradiate with ultraviolet light.
Before entering the aseptic unit there should be rubber mats that are moistened with a disinfectant solution once per shift. The aseptic block is separated from other pharmacy premises by airlocks.
Personnel requirements . Persons involved in the preparation of medicines under aseptic conditions must strictly observe the rules of personal hygiene. When entering the airlock, they must put on special shoes, wash their hands with soap and a brush, put on a sterile gown, a 4-layer gauze bandage, a cap (while carefully removing hair), and shoe covers. It is optimal to use a helmet and overalls. The gauze dressing should be changed every 4 hours. After putting on sterile technological clothing, personnel must rinse their hands with water for injection and treat them with a disinfectant solution of 80% ethyl alcohol, a solution of chlorhexidine digluconate in 70% ethyl alcohol or a 0.5% solution of chloramine B (in the absence of other substances). Entry from the airlock into the room for preparing and packaging medicines under aseptic conditions in non-sterile sanitary clothing is prohibited. It is also prohibited to go beyond the aseptic block in sterile sanitary clothing.
Sanitary clothing, gowns, gauze, textile products, cotton wool are sterilized in containers in steam sterilizers at a temperature of 132 °C for 20 minutes or at 120 °C for 45 minutes and stored in closed containers for no more than 3 days. Shoes are disinfected outside before and after work and stored in locks. Persons with infectious diseases, open wounds on skin, carriers pathogenic microflora They should not be allowed to work until they have fully recovered.
STERILIZATION
Sterilization (or sterilization)- This is the process of complete destruction of microorganisms and their spores in medicinal substances, dosage forms, on dishes, auxiliary materials, tools and apparatus.
The term “sterilization” comes from Lat. sterilis, which means barren. Sterility is achieved by observing asepsis and using sterilization methods in accordance with the requirements of the State Federal University “Methods and conditions of sterilization”, previously in the State Fund XI - article "Sterilization".
When choosing a method and duration of sterilization, it is necessary to take into account the properties, volume or weight of the materials being sterilized.
Sterilization methods can be divided into: physical, mechanical, chemical.
Physical methods sterilization. These include: thermal, or thermal, sterilization, sterilization with ultraviolet rays, radiation sterilization, sterilization with high-frequency currents.
Of these methods, thermal sterilization and ultraviolet sterilization are used in pharmacies. Other methods of sterilization in pharmacies have not yet found application.
Thermal sterilization. With this sterilization method, the death of microorganisms occurs under the influence of high temperature due to the coagulation of proteins and the destruction of enzymes of microorganisms. Sterilization with dry heat and steam is most widely used in pharmacy practice.
Steam sterilization under pressure is carried out in steam sterilizers (autoclaves) various designs. The most convenient are those steam sterilizers that automatically maintain the specified pressure and temperature, and also provide the ability to dry the auxiliary material (cotton wool, filter paper, gauze, etc.) after sterilization (Table 31). Currently, sterilizers of the type VK-15, VK-30 (Fig. 137), GP-280, etc. are widely used. In the practice of hospital pharmacies, sterilizers of the type GP-400, GPD-280 can also be used \ and GPS-500, which are similar in design and principle of operation to the GP-280 sterilizer.
At CRA No. 3 they use a VK-75 sterilizer-autoclave. Vertical steam sterilizers VK-ZO and VK-75 differ in the capacity of the sterilization chamber. They consist of a housing with a sterilization and water-steam chamber, a lid, a casing, electric heating elements, an electrical panel, an electrical contact pressure gauge, a pressure-vacuum gauge, an ejector, a safety valve, a water-indicating column and a pipeline with valves. The sterilization and water-steam chambers are combined into a single welded structure, but are functionally separated, as a result of which it is possible to shut off the flow of steam into the sterilization chamber during loading and unloading of the autoclave, as well as automatically maintain the operating pressure in the water-steam chamber for subsequent sterilization. Both chambers are made of stainless steel. The maximum steam pressure in the sterilization chamber is 0.25 MPa. Both sterilizers operate from a three-phase alternating current network with a voltage of 220/380 V.
Faculty of Pharmacy
__________________________
Department of Pharmaceutical Chemistry and Pharmacognosy
Analysis medicines,
Derivatives of 5-nitrofuran.
Educational - Toolkit for students
Faculty of Pharmacy.
Purpose of the lesson:
Study the properties, identification reactions and methods of quantitative determination of medicinal substances derived from furan;
Lesson objectives:
Answer questions from incoming inspection;
To study the properties of medicinal substances of the furan group: nitrofuran, nitrofurantoin, furazolidone, furagin;
Carry out their identification reactions in accordance with the requirements of the RD;
Determine the quantitative content of nitrofuran in the substance using reverse iodometry;
In the process of self-study and in class, the student must acquire the following knowledge and skills:
Know:
Chemical nomenclature of medicinal substances, furan derivatives;
Formulas, Russian, international non-proprietary, names of medicinal substances used in medical practice: nitrofural, nitrofurantoin, furazolidone, furagina;
Identification reactions of nitrofural, nitrofurantoin, furazolidone, furagin;
Methods for the quantitative determination of nitrofural, nitrofurantoin, furazolidone, furagin;
Conditions for storage and use in medical practice of nitro-fural, nitrofurantoin, furazolidone, furagin
Be able to
Assess the quality of medicinal substances, furan derivatives according to appearance and solubility.
Determine the identity of nitrofuran;
Assess the quantitative content of nitrofuran;
Lesson assignment:
Analysis of the good quality of medicinal substances of furan derivatives - nitrofuran.
Perform reactions confirming the ability of drugs to ionize and form salts.
Determine the quantitative content of nitrofuran in the substance using reverse iodometry and photocolorimetry.
Task No. 1. Conduct a pharmacopoeial analysis of the furatsilin substance.
Description.
Yellow or greenish-yellow fine-crystalline powder, odorless, bitter taste.
Authenticity.
Dissolve 0.01 g of the substance in a mixture of 5 ml of water and 5 ml of sodium hydroxide solution. An orange-red color appears. The resulting solution is heated to a boil and wet red litmus paper is added to the vapor. The ammonia released during the decomposition of the substance is detected by the blueness of red litmus paper.
Weight loss on drying.
About 1.0 g of the substance (exactly weighed) is dried at a temperature of 100 to 105ºС to constant weight. The weight loss during drying should not exceed 0.5%.
Semicarbazide.
10 ml of the same filtrate is heated and 2 m of Fehling’s reagent, preheated to boiling, is poured in; the color of the solution gradually turns from yellow to dark green; Within an hour, no red precipitate of cuprous oxide should form.
quantitation
Iodometric determination (according to the Global Fund)
About 0.1 g of the substance (exactly weighed) is placed in a 500 ml volumetric flask, 4 g of sodium chloride, 300 ml of water are added and dissolved by heating to 70-80ºC in a water bath. The cooled solution is brought to the mark with water and mixed. To 5 ml of 0.01 M iodine solution placed in a 50 ml flask, add 0.1 ml of sodium hydroxide solution and 5 ml of the test solution. After 1-2 minutes, 2 ml of diluted sulfuric acid is added to the solution and the released iodine is titrated from a microburette with a 0.01 M solution of sodium thiosulfate (starch as indicator).
At the same time, a control experiment is carried out.
1 ml of 0.01 M iodine solution corresponds to 0.0004954 g of furatsilin, which must be at least 97.5%.
Spectrophotometric determination (according to ND)
About 0.075 g (exactly weighed) of the substance is placed in a 250 ml volumetric flask, dissolved in 30 ml of dimethylformamide, the volume of the solution is adjusted to the mark with water and mixed. 5 ml of the resulting solution is placed in a 250 ml volumetric flask, the volume of the solution is adjusted to the mark with water and mixed. The optical density of the resulting solution is measured using a spectrophotometer at a wavelength of 375 nm in a cuvette with a layer thickness of 10 mm. At the same time, measure the optical density of a solution of GSO furatsilin, prepared from a sample of 0.075 g of GSO furatsilin, similar to the test solution.
Water is used as a reference solution.
where: D 1 is the optical density of the test solution;
D 0 - optical density of the solution of GSO furatsilin;
a 0 – mass of GSO furacilin, g;
A - mass of substance, g;
Task No. 2. Conduct a pharmacopoeial analysis of furatsilin tablets.
Furacilin tablets 0.1 g
Composition per tablet:
Furacilina 0.1 g
Excipients to obtain a tablet weighing 0.3 g
Description. Tablets are yellow or greenish-yellow.
Authenticity. 0.03 g of powdered tablets give authenticity reactions characteristic of furatsilin.
Quantitation. About 0.06 g (exactly weighed) of powdered tablets is placed in a glass with a capacity of 20-25 ml, 1.5 ml of water saturated with furatsilin is added, mixed with a glass rod and filtered. The remainder in the glass is washed with 1 ml of water saturated with furatsilin. The filter with the precipitate is placed in a 100 ml volumetric flask, the precipitate remaining in the glass is washed off with warm water, 0.8 g of sodium chloride, 70 ml of water are added and dissolved by heating to 70-80 0 C in a water bath. The cooled solution is brought to the mark with water and mixed.
Furacilin (furatsin, nitrofuran, nitrofurazone, 5-nitrofurfurylidenesemicarbazone) C6H6O4N4.
It is a yellow or greenish-yellow crystalline powder, odorless, bitter in taste. Melts at a temperature of 227-232°C with decomposition. Furacilin is very slightly soluble in water (1:4200), slightly soluble in 95% alcohol, practically insoluble in ether, soluble in alkalis. The solution is yellow or colorless. Aqueous solutions lose their antimicrobial activity during long-term storage.
The starting product for the synthesis of all drugs of the nitrofuran series is a very accessible substance - furfural, obtained from waste of various agricultural products (corn cobs, sunflower husks).
The production of furatsilin is based on the nitration of furfural in a mixture of acetic anhydride and acetic acid. The resulting 5-nitrofurfural diacetate is hydrolyzed and the resulting 5-nitrofurfural is condensed with semicarbazide hydrochloride:
Methods for identifying furatsilin
To test authenticity, IR spectra of nitrofuran derivatives are used. They are pressed into tablets with potassium bromide and spectra are recorded in the region of 1900-1700 cm-1. The IR spectra must completely coincide with the IR spectra of the GSO. The IR spectrum of furatsilin has absorption bands at 971, 1020, 1205, 1250, 1587, 1784 cm-1.
Chemical reactions used to identify furatsilin.
The authenticity of furatsilin is determined by color reaction with aqueous solution sodium hydroxide. When using dilute alkali solutions, nitrofural forms an orange-red-colored acisol:
When furatsilin is heated in solutions of alkali metal hydroxides, the furan ring breaks and forms sodium carbonate, hydrazine and ammonia. The latter is detected by a change in color of wet red litmus paper:
Characteristic color reactions that allow 5-nitrofuran derivatives to be distinguished from each other are produced by an alcohol solution of potassium hydroxide in combination with acetone: nitrofural acquires a dark red color.
Furacilin is also identified using general reaction formation of 2,4-dinitrophenylhydrazone (melting point 273°C). It precipitates when the solution is boiled medicinal substance in dimethylformamide with a saturated solution of 2,4-dinitrophenylhydrazine and 2 M hydrochloric acid solution. A solution of nitrofural in dimethylformamide after adding a freshly prepared 1% solution of sodium nitroprusside and 1 M sodium hydroxide solution gives a red color.
Nitrofuran derivatives form colored insoluble complex compounds with salts of silver, copper, cobalt and other heavy metals in a slightly alkaline environment. When a 1% solution of copper (II) sulfate, a few drops of pyridine and 3 ml of chloroform are added to a solution of nitrofurantoin (in a mixture of dimethylformamide and water), after shaking, the chloroform layer acquires a green color. Complex compounds of nitrofural and furazolidone under these conditions are not extracted by chloroform.
Redox reactions (formation of a “silver mirror”, with Fehling’s reagent) can be performed after alkaline hydrolysis, accompanied by the formation of aldehydes.
