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LECTURE № 5 Halogenderivatives of hydrocarbons, which are used in the medical practice. Some alcohols, aldehydes and ethers as drugs associate prof. Mosula L. M. The Plan 1. Halogenderivatives of hydrocarbons : Ethyl Chloride, Chloroform, Iodoform, Fluothane. 2. Alcohol - Ethanol. 3. Ether – Anaesthetic ether. 4. Aldehyde - Formaldehyde. Halogenderivatives of hydrocarbons as drugs Ethyl Chloride Aethylii chloridum C2H5Cl M.m. = 64,52 g/mol Aethylium chloridum Aethylium chloratum Aethylis Chloridum* Aether chloratus H3C-CH2Cl (C2H5Cl) 64.52 The chemical name: ethyl chloride, chloroethane. It may be prepared by the action of hydrogen chloride on ethanol or on Industrial Methylated Spirit; in the later case it may contain a small variable of methyl chloride. Obtaining 1. Heating (110-120) absolute ethyl alcohol with dry HCl (or concentrated HNO3) in the presence of dehydrating means (CaCl2 anhydrous, ZnCl2 or conc. H2SO4): C2H5OH + HCl C2H5Cl + H2O 2. Hydrochlorination of ethylene: Н2С=СН2 + HCl = H3C–CH2Cl 3. Chlorination ethane: C2H6 + Cl2 C 2H5Cl + HCl Characteristics. Gaseous at ambient temperature and pressure, but usually compressed to a colorless, mobile, flammable and very volatile liquid; odour, ethereal. Slightly soluble in water, miscible with ethanol and with ether. Identification. A. Burns with a luminous flame with the production of hydrogen chloride. C2H5Cl + 2O2 = CO2 + 2H2O + HCl B. Vigorously shake 2 ml with 5M sodium hydroxide and warm on a water bath. Reserve a portion of the solution for test C. To the resulting solution add 2 ml of iodinated potassium iodide solution and warm. Crystals of iodoform are produced (iodoform test).. or C2H5Cl + NaОН C2H5ОН + NaCl C2H5OH + 4I2 + 6NaOH = CHI3 + HCOONa + 5NaI yellow precipitate and its specific smell C. The solution reserved in test B yields the reactions characteristic of chlorides. KCl + AgNO3 AgCl + KNO3 white precipitate Cl– + Ag+ AgCl AgCl + 2NH4OH Ag(NH3)2Cl + 2H2O Tests 1. Definition of temperature of boiling. 2. Density measurement. 3. Acidity. 4. Ethanol (an inadmissible impurity) which define bymeans of iodoform test (see above); there should not be a turbidity. 5. Organic impurity (an inadmissible impurity). At mixing of a preparation with concentrated sulphatic acid H2SO4 at cooling in the ice water, the received solution should be colourless. 6. The rest at evaporation. Storage. The list of strong substances. Ethyl chloride should be stored at temperature not exceeding 15*C, in the cool place protected from light. . INDICATIONS FOR USE Anaesthetic, an inhalation narcotic. For external use only Ethyl Chloride is a vapocoolant (skin refrigerant) intended for topical application to control pain associated with injections, minor surgical procedures (such as lancing boils, incisions, and drainage of small abscesses) and athletic injuries. It is also intended for the treatment of restricted motion associated with myofascial pain caused by trigger points. Contents under pressure. Store in a cool place (controlled room temperature). Do not store above 120°C. Do not store on or near high frequency ultrasound equipment. CHLOROFORM Chloroformium M =119,38 g/mol Chloroform for narcosis Chloroformium pro narcosi Chloroformium Anaesthesicum* CHCl3 The chemical name: Chloroform, trichloromethane. Cl H C Cl Cl Obtaining 1. Electrolysis solution of sodium chloride in the presence of ethanol or acetone (a modern method). This method consists of such stages. a) Electrolysis solution of sodium chloride with formation of alkali and chlorine and hydrogen gases: 2NaCl + 2HOH K (–): Na +; H2O 2H2O + 2e → 2OH - + H2 ↑ A (+): Cl–; H2O 2Cl- – 2e → Cl2 b) Reaction disproportionation of chlorine in an alkali solution: NaOH + Cl2 = NaCl + NaClO + H2O c) Oxidation of ethanol or acetone* by means of sodium hypochlorite NaClO to acetic aldehyde or acetone trichloride (*then use acetone receive purer chloroform): C2H5OH H3C C + O +1 NaClO CH3 H3C C H acetic aldehyde + 3 NaClO + H3C -1 NaCl C CCl3 + H2O + 3 NaOH O acetone trichloride O acetic aldehyde further is oxidised to trichloroacetaldehyde: O H3C C H O + 3 NaClO CCl3 C + H trichloroacetaldehyde Thus, the total equation of oxidation of ethanol: C2H5OH + 4NaClO Cl3CCНO + 3NaOH + NaCl + H2O 3 NaOH d) Decomposition acetone trichloride or trichloroacetaldehyde by means of alkali with chloroform formation: O CCl3 C H O + NaOH CHCl3 + H C ONa chloroform sodium formiate O H3C C O CCl3 + NaOH CHCl3 + chloroform H3C C ONa sodium acetate 2. Alkali action on chloral hydrate (receive purer chloroform): OH CCl3 C H OH O + NaOH CHCl3 + HC ONa + H2O 4. Reduction tetrachlormethane by iron in the presence of water. ССl4 + Fe + HOH → CHCl3 + FeOHCl Chloroform clearing. Chloroform for narcosis Chloroformium pro narcosi receive similarly to chloroform with that distinction, that it subject to additional clearing by fractional clearing at temperature 70 With, thus impurity remain in a solution. DEFINITION Chloroform is trichloromethane to which either 1.0 to 2.0% of ethanol or 50 mg per litre of amylene has been added. CHARACTERISTICS A colourless, volatile liquid. Slightly soluble in water ; miscible with absolute ethanol , with ether , with fixed and volatile oils and with most organic solvents. IDENTIFICATION A. The infrared absorbtion spectrum. B. Heat with alcoholic solution of alkali (potassium hydroxide). Obtained solution yields reactions characteristic of chlorides. CHCl3 + 4KOH → 3KCl + НСООК + 2Н2О a) Chlorides-ions: with solution of AgNO3: Сl–+ Ag + → AgCl ↓ white AgCl + 2NH4OH = [Ag (NH3) 2] Cl + 2H2O b) Potassium formiate НСООК: with Feling reagent Фелинга - formation of red precipitate Cu2O: НСООК + 2CuO + KOH = K2CO3 + Cu2O +Н2О red Reaction with phenols: the product of condensation with resorcinol has red colouring, and with β- naphthol – dark blue. TESTS Distillation range Not more than 5.0% v/v distils below 60° and the remainder distils at 60° to 62°, Appendix V C. Weight per ml 1.474 to 1.479 g, Appendix V G. Acidity or alkalinity Shake 10 ml with 20 ml of freshly boiled and cooled water for 3 minutes and allow to separate. To 5 ml of the aqueous layer add 0.1 ml of neutral litmus solution. The colour produced is the same as that produced on adding 0.1 ml of the neutral litmus solution to 5 ml of freshly boiled and cooled water . Chloride To 5 ml of the aqueous layer obtained in the test for Acidity or alkalinity add 5 ml of water and 0.2 ml of silver nitrate solution. The solution is clear, Appendix IV A. Free chlorine To 10 ml of the aqueous layer obtained in the test for Acidity or alkalinity add 1 ml of a 5.0% w/v solution of zinc iodide and 0.1 ml of starch mucilage. No blue colour is produced. Aldehyde Shake 5 ml with 5 ml of water and 0.2 ml of alkaline potassium tetraiodomercurate solution in a glassstoppered flask and allow to stand in the dark for 15 minutes. Not more than a pale yellow colour is produced. Ethanol Carry out the following test for Chloroform that contains ethanol. Carry out the method for gas chromatography, Appendix III B, injecting 0.1 µl of each of the following solutions. Solution (1) contains 1.0% v/v of absolute ethanol and 1.0% v/v of propan-1-ol (internal standard) in water . Solution (2) is the substance being examined. Solution (3) contains 1.0% v/v of the internal standard in the substance being examined. The chromatographic procedure described under Related substances may be used. The test is not valid unless the height of the trough separating the ethanol peak from the chloroform peak in the chromatogram obtained with solution (2) is less than 15% of the height of the ethanol peak. Calculate the percentage content of ethanol from the areas of the peaks due to ethanol and the internal standard in the chromatograms obtained with solutions (1) and (3). Non-volatile matter 25 ml, when evaporated to dryness and dried at 105°, leaves not more than 1 mg of residue. IMPURITIES A. carbon tetrachloride, B. dichloromethane, C. bromochloromethane ASSAY. Pharmacopoeia quantitative definition does not demand, but it is possible to use reaction with spirit solution of alkali for the back acid-base titration. To defined volume of investigated substance add excess of standard solution of alkali KOH: CHCl3 + 4KOH → НСООК + 3KCl + 2H2O excess Not reacted KOH titrate by standard solution of НСl in the presence of methyl orange colouring before transition from yellow to the pink. T KOH + HCl → KCl + H2O rest Em (CHCl3) = M. m./4 STORAGE Chloroform should be kept in a well-closed container with a glass stopper or other suitable closure and protected from light. LABELLING The label states whether it contains ethanol or amylene. Action and use General anaesthetic; antimicrobial preservative. Preparations Chloroform Spirit Chloroform Water Double-strength Chloroform Water IODOFORM Iodoformium CHI3 Formylum triiodatum Obtaining Obtaining methods iodoform are similar to methods of obtaining of chloroform. 1. Electrolysis solution of potassium iodide at the presence of sodium carbonate and ethanol: 2КI + 2HOH H2 + I2 + 2KOH K (–): K +; H2O 2H2O + 2e → 2OH - + H2 ↑ A (+): I–; H2O 2I - – 2e → I2 4I2 + C2H5OH + 3Na2CO3 CHI3 + HCOONa + 5NaI + 3CO2 + 2H2O yellow 2. Interaction crystal iodine with ethanol in solution of sodium carbonate (at 70C). Brown colouring quickly disappears and is formated CHI3 in the form of yellow precipitate. 3. Interaction crystal iodine with acetone in solution of sodium carbonate (it is similar to chloroform): 3I2 + CH3СОCH3 + 2Na2CO3 CHI3 + 3CH3COONa + 3NaI + 2CO2 + H2O CHARACTERISTICS Iodoform is a yellow crystalline powder (m.p. 116120ºC); odor characteristic; Insoluble in water, practically insoluble in alcohol, ether, chloroform. Identification 1. Decomposition (oxidation) of a substance. Heat in the test tube. The violet vapor of I2 is produced: 2CHI3 + 2O2 = 3I2 + CO + CO2 + H2O violet vapor 2. Saponification by means of alcoholic solution of alkali. CHI3 dissolve in alcoholic solution of alkali KOH, and then the received solution acidify by HNO3; yellow colouring of I2 is formed: CHI3 + 4KOH → 3KI + НСООК + 2Н2О 6KI + 8HNO3 = 2I2 + 6KNO3 + 2NO + 2H2O yellow Tests for cleanliness. 1. Impurity of mineral acids, dyes (inadmissible impurity). At vigorous stirring of a preparation with water and filtration the filtrate should be colourless. 2. The maintenance of impurity of chlorides, sulphates within standards. ASSAY. Argentometry, Volhard method. Shot of substance dissolve in spirit, add excess of a standard solution AgNO3, acidify by HNO3, heat up on a water heater within 30 minutes, protecting a reactionary mix from light. Excess of AgNO3 titrate by standard solution of ammonium thiocyanate NH4SCN in the presence of the indicator (NH4) Fe (SO4) 2 before pink colouring. In parallel spend control experience. CHI3 + AgNO3 + H2O = AgI + 3HNO3 + CO excess yellow T AgNO3 + NH4SCN = AgSCN + NH4NO3 T white 3NH4SCN + (NH4) Fe (SO4) 2 = Fe (SCN) 3 + 2 (NH4) 2SO4 Ind pink colouring Еm = M.м. Storage In well corked containers, in banks of dark colour, in the cool place protected from light for the prevention of decomposition of a preparation. Action and use. An external antiseptic(ointment). FLUOTHANE (Halothane) F3C-CHClBr Phthorothanum Halothanum* M. m. = 197,39 g/mol CH(Br)ClCF3 (2-Bromo-2-chloro-1,1,1-trifluoroethane) Halotane, a volatile halohenated hydrocarbon (b.p. 50*C), is now taken as a standard inhalation anesthetic agent. Obtaining 1. Bromination of 1,1,1-trifluoro-2-chloroethane at 465 C: F3C–CH2Cl + Br2 = F3C–CHClBr + HBr Properties Description. Transparent, colourless, a heavy, mobile liquid with a smell reminding a smell of chloroform. Has sweet and burning taste. Does not burn and does not ignite, does not blow up in a mix with air and with an aether (to 13 %). Contains 0,01 % мас. The stabilizer тимола. Solubility. Slightly soluble in water (0,345 %). Mixes up with waterless spirit, ether, chloroform, oils (flying and nonvolatile), trichloroethylene. Identification 1. Measurement of physical constants: Definition of temperature of boiling. The temperature of boiling (distillation) is equal 49–51 C. Measurement of relative density. The relative density at 20 With is equal 1,865–1,870/ml Having the big density, фторотан, unlike chloroform and трихлорэтилена, at addition of the concentrated sulphatic acid is in the bottom layer. Measurement of an indicator of refraction. The refraction indicator at 20 With is equal 1,3695–1,3705. 2. IR-spectroscopy. IR-spectrum of drug should correspond to IRspectrum the standard sample of fluothane. 3. Identification of Fluorine (after fusion with metal sodium) by means of mix of zirconium nitrate and alizarine red (alizarine S). Technique. 0,5 ml of a preparation heat up with 0,05 г the fused metal sodium, cool, cautiously add 2 ml of water, a solution filter and to a filtrate add 0,5 ml ice СН3СООН. 0,1 ml of this solution add to 0,2 ml of the mix consisting from identical volume fresh prepare of a solution alizarine S and 0,1 % solution of zirconium nitrate in chloride acid; change of red colouring of a solution in light yellow owing to formation of very steady complex compound Na2ZrF6 is observed. High quality In a drug there should be no a chlorides-, bromides-ions, and also free chlorine and bromine. As conserving agent use thymol, which in a drug should be 0,01 %. ASSAY of thymol (stabilizer) by means of colorimetry, on the basis of reaction with the titan (IV) oxide TiO2, comparing intensity of colouring with a standard solution. Storage. The list of strong substances. In dense corkin bottles (on 50 and 250 ml) from dark glass, in the dry, cool place protected from light (under the influence of light slowly decays). Every 6 months the preparation is subject to repeated check. Application. Means for an inhalation narcosis Alcohols and ethers as drugs Various alcohols have been used as antiseptics and disinfectants. Antibacterial potencies of primary alcohols increase with molecular weight up to C8. Beyond this point, water solubility is less than the minimum effective concentration, and the apparent potency decreases with molecular weight. Branching decreases antibacterial potency; hence, the isomeric alcohols follow the order primary > secondary > tertiary. Noneseless, isopropylalcohol is used commercially instead of normal propyl alcohol, because it is cheaper. Isopropyl alcohol is slightly more active than ethyl alcohol against vegetative bacterial growth, but alcohola are largely ineffective against spores. Alcohol ( C2H5OH, ethanol, spiritus vini rectificatus, wine spirit) is a clear, colorless, volatile liquid having a burning taste and characteristic pleasant odour. It is flammable and miscible with water and most organic solvents. The commercial product contains about 95% ethanol by volume because this concentration forms an azeotrope that distills at 78.2*F. Alcohol has been known for centuries as a fermentation product from grain and other carbohydrate sources. It can also be prepared synthetically by the sulphuric acid-catalyzed hydration of ethylene. ETHANOL C2H5OH ETHANOL (96 PER CENTUM) Ethanolum (96 per centum) Ethanolum anhydricum ETHANOL, ANHYDROUS Absolute Alcohol; Dehydrated Alcohol М.м. = 46,07 г/моль (Anhydrous Ethanol, Ph Eur monograph 1318) C2H6O 46.07 64-17-5 Ph Eur DEFINITION Content Not less than 99.5 per cent V/V of C2H6O (99.2 per cent m/m), at 20 °C, calculated from the relative density using the alcoholimetric tables (5.5). Obtaining 1. Fermentation of natural sugary substances (grape juice, a potato, grain and other starchconteining raw materials). a) From glucose under the influence of enzymes zymases, containing in yeast, at temperature 30-35C: C6H12O6 2C2H5OH + 2CO2 b) With starchconteining raw materials: 2 (C6H10O5) n + nН2O nС12H22O11 starch maltose Further under the influence of enzymes maltase maltose hydrolyzes to glucose: nС12H22O11 + H2O 2 nC6H12O6 maltose glucose Glucose under the influence of group of enzymes zymases gives end-products of fermentation – ethanol С2H5OH and carbonic gas СО2: 2nC6H12O6 4nС2H5OH + 4nCO2 аmylase,t 600 C maltase zymases, 30350 2. Synthetic methods a) Hydration ethylene under a high pressure: Н2С=СН2 + НОН Н 3С–СН2ОН p Or H2C CH2+ HC HO HO S O O O H3C CH2 O S OH +HOH H3C CH2 OH + H2SO4 O ethylsulphate acid b) From acetylene on Kucherov reaction with the subsequent reduction acetic aldehyde to spirit: CH + HOH Hg2+ H+ OH H2C CH vinyl alcohol tautomerism O H3C C H acetic aldehyde Acetic aldehyde drive away and restore hydrogen Н2 in the presence of catalysts (N і, HgSO4) to alcohol: O Ni H3C CH2 OH H3C C + H2 H CHARACTERS Appearance Colourless, clear, volatile, flammable liquid, hygroscopic. Solubility Miscible with water and with methylene chloride. It burns with a blue, smokeless flame. bp: about 78 °C. IDENTIFICATION First identification A, B. Second identification A, C, D. A. It complies with the test for relative density (see Tests). B. Infrared absorption spectrophotometry (2.2.24). Comparison ethanol . Ph. Eur. reference spectrum of anhydrous C. Mix 0.1 ml with 1 ml of a 10 g/l solution of potassium permanganate R and 0.2 ml of dilute sulphuric acid R in a test-tube. Cover immediately with a filter paper moistened with a freshly prepared solution containing 0.1 g of sodium nitroprusside R and 0.5 g of piperazine hydrate R in 5 ml of water R. After a few minutes, an intense blue colour appears on the paper and becomes paler after 10-15 min. 5C2H5OH + 2KMnO4 + 3H2SO4 → 2MnSO4 + 5CH3CHO + K2SO4 + 8H2O MnO4– + 8H+ + 5е Mn2+ + 4H2O |5|2 C2H6O – 2е C2H4O + 2H+ |2|5 5C2H5OH + 2MnO4– + 6H+ 2Mn2+ + 5CH3CHO + 8H2O D. To 0.5 ml add 5 ml of water R, 2 ml of dilute sodium hydroxide solution R, then slowly add 2 ml of 0.05 M iodine. A yellow precipitate is formed within 30 min. C2H5OH + 4I2 + 6NaOH CHI3 + 5NaI + HCOONa + 5H2O yellow Formation ethylacetate. At heating of drug with CH3COOH and concentrated sulphatic acid H2SO4 it is formed ethyl-atcetic ester with a characteristic fruit smell (a smell of pears): O O H3C CH2 OH + H2SO4 C HO CH3 conc. H3C CH2 O C CH3 + H2O TESTS Appearance It is clear (2.2.1) and colourless (2.2.2, Method II) when compared with water R. Dilute 1.0 ml to 20 ml with water R. After standing for 5 min, the dilution remains clear (2.2.1) when compared with water R. Acidity or alkalinity To 20 ml add 20 ml of carbon dioxide-free water R and 0.1 ml of phenolphthalein solution R. The solution is colourless. Add 1.0 ml of 0.01 M sodium hydroxide. The solution is pink (30 ppm, expressed as acetic acid). Relative density (2.2.5) 0.805 to 0.812. Absorbance (2.2.25) Maximum 0.40 at 240 nm, 0.30 between 250 nm and 260 nm and 0.10 between 270 nm and 340 nm. Examine between 235 nm and 340 nm, in a 5 cm cell using water R as the compensation liquid. The absorption curve is smooth. Residue on evaporation Maximum 25 ppm m/V. Evaporate 100 ml to dryness on a water-bath and dry at 100-105 °C for 1 h. The residue weighs a maximum of 2.5 mg. IMPURITIES A. 1,1-diethoxyethane (acetal), B. acetaldehyde, C. Acetone ASSAY 1. Relative density (2.2.5) 0.805 to 0.812. 2. Iodometry. Ethanol oxidise by solution K2Cr2O7 in the medium of H2SO4 Excess of K2Cr2O7 establish by iodometry (the indicator – starch). K2Cr2O7 + 3C2H5OH + 4H2SO4 → Cr2 (SO4)3 + 3CH3CHO + K2SO4 + 7H2O excess Cr2O72– + 14H+ + 6е 2Cr3+ + 7H2O |6|3|1 C2H6O – 2е C2H4O + 2H+ |2|1|3 K2Cr2O7 + 6KI + 7H2SO4 Cr2 (SO4)3 + 3I2 + 4K2SO4 + 7H2O excess Cr2O72– + 14H+ + 6е 2Cr3+ + 7H2O | 6 | 3 | 1 2I– – 2е I2 |2|1|3 T I2 + 2Na2S2O3 NaI + Na2S4O6 2I– – 2е I2 2S2O32– – 2е S4O62– Em(C2H5OH) = М.м./4 3. In drugs recommend to define concentration of alcohol on density or behind boiling temperature. STORAGE Protected from light. In densely corked containers, in a cool place. Application. External antiseptic and irritating means. ANAESTHETIC ETHER Aether for narcosis Aether anaestheticus ANAESTHETIC Aether medicinalis M. m. = 74,12 g/mol Aether medical Aether pro narcosi Aether aethylicus Aether ethyl H5C2-O-C2H5 The chemical name: diethyl ether, ethoxy ethane. C4H10O (CH3-CH2-O-CH2-CH3) DEFINITION Diethyl ether. It may contain a suitable non-volatile antioxidant at an appropriate concentration. CHARACTERS Appearance Clear, colourless liquid, volatile, very mobile. Solubility Soluble in 15 parts of water, miscible with ethanol (96 per cent) and with fatty oils. It is highly flammable. IDENTIFICATION A. (BrPh, SPU, add. 1). Relative density 0.714 to 0.716. B. (BrPh, SPU, add. 1). Distillation range 34.0 °C and 35.0 °C. ASSAY not makes, according to Pharmacopoeia. STORAGE Protected from light, in the dense corked containers , protected from light, at a temperature not less then 8 °C and not more then 15 °C. Action and use General anaesthetic. Browse: British Pharmacopoeia 2009 SPU, add. 1 Formaldehyde Solution (Formaldehyde Solution (35 per cent), Ph Eur monograph 0826) Formaldehydi solutio (35 per centum) FORMALDEHYDE SOLUTION (35 PER CENT) Formalinum CH2O 30.03 DEFINITION Content 34.5 per cent m/m to 38.0 per cent m/m of formaldehyde (CH2O; Mr 30.03). It contains methanol as stabiliser. OBTAINING Methane oxidation: 2 CH4 + O2 2 CH3OH O2 O 2H C CHARACTERS Appearance Clear, colourless liquid. Solubility Miscible with water and with ethanol (96 per cent). It may be cloudy after storage. H + 2 H2O IDENTIFICATION A. (BrPh, SPU, add. 1). Reaction with chromotropic acid sodium salt in the sulphuric-acid medium Dilute 1 ml of solution S (see Tests) to 10 ml with water R. To 0.05 ml of the solution add 1 ml of a 15 g/l solution of chromotropic acid sodium salt R, 2 ml of water R and 8 ml of sulphuric acid R. A violet-blue or violet-red colour develops within 5 min. SO3H HO3S SO3Na HO + 2 HO SO3Na HO HC O H H2SO4 кон ц. HO C H2 HO OH SO3H HO3S SO3H HO3S C H HO O OH SO3H HO3S OH [O] H2O B. (BrPh, SPU, add. 1). Reaction with phenylhydrazine hydrochloride and potassium ferricyanide solution To 0.1 ml of solution S add 10 ml of water R. Add 2 ml of a 10 g/l solution of phenylhydrazine hydrochloride R, prepared immediately before use, 1 ml of potassium ferricyanide solution R and 5 ml of hydrochloric acid R. An intense red colour is formed. 2 N H NH2 * HCl + N N C H2 CH2O N - H2O N H N H C H2 N H N H K3[Fe(CN)6] N C. (BrPh, SPU, add. 1). Reaction of “silver mirror” Mix 0.5 ml with 2 ml of water R and 2 ml of silver nitrate solution R2 in a test-tube. Add dilute ammonia R2 until slightly alkaline. Heat on a water-bath. A grey precipitate or a silver mirror is formed. 2AgNO3 + 2NH4OH = [Ag(NH3)2]NO3 + 2H2O НCНO + 2[Ag(NH3)2]NO3 + H2O = 2Ag + НCOONH4 + NH3 + 2NH4NO3 D. (BrPh, SPU, add. 1). It complies with the limits of the assay. ASSAY Iodometry in the alkaline medium, back titration I20 + 2 NaOH = NaI-1 + NaI+1O + H2O NaI-1 + 1NaІ+1O + H2SO4 = 1I20 + Na2SO4 + H2O 1I2 + 2Na2S2O3 = 2NaІ + Na2S4O6 Em(HCHO) = M. m./2 * Alkaline medium necessary because in the acid medium at interaction iodine I2 with formaldehyde НСНО iodide acid НI is formed, which is reducing agent and reaction has back direction. STORAGE Protected from light, at a temperature of 15 °C to 25 °C. Ph Eur Action and use When suitably diluted, used in the treatment of warts. Ph Eur Thanks for attention!