Приложение 13 Частные фармакопейные статьи для лс альдегидов и углеводов

(ЕР)

Formaldehyde Solution

Formalin

NOTE: The name Formalin as a synonym for Formaldehyde Solution may be used freely in many countries,including the United Kingdom, but in other countries exclusive proprietary rights in this name are claimed.

CH2O 30.03

Action and use Used in the treatment of warts.

DEFINITION

Formaldehyde solution (35 per cent) contains not less than 34.5 per cent m/m and not more than

38.0 per cent m/m of formaldehyde (CH2O; Mr 30.03) with methanol as stabiliser.

CHARACTERS

A clear, colourless liquid, miscible with water and with alcohol. It may be cloudy after storage.

IDENTIFICATION

A. 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.

B. 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.

C. 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.

D. It complies with the limits of the assay.

TESTS

Solution S Dilute 10 ml, filtered if necessary, to 50 ml with carbon dioxide-free water R.

Appearance of solution Solution S is colourless (Method II, 2.2.2).

Acidity To 10 ml of solution S add 1 ml of phenolphthalein solution R. Not more than 0.4 ml of 0.1M sodium hydroxide is required to change the colour of the indicator to red.

Methanol 9.0 per cent V/V to 15.0 per cent V/V, determined by gas chromatography (2.2.28) using

ethanol R1 as internal standard.

Internal standard solution. Dilute 10 ml of ethanol R1 to 100 ml with water R.

Test solution. To 10.0 ml of the solution to be examined add 10.0 ml of the internal standard solution and dilute to 100.0 ml with water R.

Reference solution. To 1.0 ml of methanol R add 10.0 ml of the internal standard solution and dilute to 100.0 ml with water R.

The chromatographic procedure may be carried out using:

— a glass column 1.5 m to 2.0 m long and 2 mm to 4 mm in internal diameter, packed with

ethylvinylbenzene-divinylbenzene copolymer R (150 μm to 180 μm),

— nitrogen for chromatography R as the carrier gas at a flow rate of 30 ml to 40 ml per minute,

— a flame-ionisation detector,

maintaining the temperature of the column at 120°C and that of the injection port and of the

detector at 150°C.

Inject 1 μl of the reference solution. Adjust the sensitivity of the detector so that the heights of the

peaks in the chromatogram obtained are not less than 50 per cent of the full scale of the recorder.

The test is not valid unless the resolution between the peaks corresponding to methanol and ethanol

is at least 2.0. Inject separately 1 μl of the test solution and 1 μl of the reference solution. Calculate

the percentage content of methanol.

Sulphated ash (2.4.14). Not more than 0.1 per cent, determined on 1.0 g.

ASSAY

Into a 100 ml volumetric flask containing 2.5 ml of water R and 1 ml of dilute sodium hydroxide

solution R, introduce 1.000 g of the solution to be examined, shake and dilute to 100.0 ml with

water R. To 10.0 ml of the solution add 30.0 ml of 0.05M iodine. Mix and add 10 ml of dilute sodium hydroxide solution R. After 15 min, add 25 ml of dilute sulphuric acid R and 2 ml of starch solution R.

Titrate with 0.1M sodium thiosulphate.

1 ml of 0.05M iodine is equivalent to 1.501 mg of CH2O.

STORAGE

Store in a well-closed container, protected from light, at a temperature of 15°C to 25°C.

Chloral Hydrate

C2H3Cl3O2 165.4

Action and use Hypnotic.

DEFINITION

Chloral hydrate contains not less than 98.5 per cent and not more than the equivalent of 101.0 per

cent of 2,2,2-trichloroethane-1,1-diol.

CHARACTERS

Colourless, transparent crystals, very soluble in water, freely soluble in alcohol and in ether.

IDENTIFICATION

A. To 10 ml of solution S (see Tests) add 2 ml of dilute sodium hydroxide solution R. The mixture

becomes cloudy and, when heated, gives off an odour of chloroform.

B. To 1 ml of solution S add 2 ml of sodium sulphide solution R. A yellow colour develops which

quickly becomes reddish-brown. On standing for a short time, a red precipitate may be formed.

TESTS

Solution S Dissolve 3.0 g in carbon dioxide-free water R and dilute to 30 ml with the same solvent.

Appearance of solution Solution S is clear (2.2.1) and colourless (Method II, 2.2.2).

pH (2.2.3). The pH of solution S is 3.5 to 5.5.

Chloral alcoholate Warm 1.0 g with 10 ml of dilute sodium hydroxide solution R, filter the supernatant solution and add 0.05M iodine dropwise until a yellow colour is obtained. Allow to stand for 1 h. No precipitate is formed.

Chlorides (2.4.4). 5 ml of solution S diluted to 15 ml with water R complies with the limit test for

chlorides (100 ppm).

Heavy metals (2.4.8). 10 ml of solution S diluted to 20 ml with water R complies with limit test A

for heavy metals (20 ppm). Prepare the standard using lead standard solution (1 ppm Pb) R.

Non-volatile residue Evaporate 2.000 g on a water-bath. The residue weighs not more than 2 mg

(0.1 per cent).

ASSAY

Dissolve 4.000 g in 10 ml of water R and add 40.0 ml of 1M sodium hydroxide. Allow to stand for

exactly 2 min and titrate with 0.5M sulphuric acid, using 0.1 ml of phenolphthalein solution R as

indicator. Titrate the neutralised solution with 0.1M silver nitrate, using 0.2 ml of potassium chromate solution R as indicator. Calculate the number of millilitres of 1M sodium hydroxide used by deducting from the volume of 1M sodium hydroxide added at the beginning of the titration the volume of 0.5M sulphuric acid used in the first titration and two-fifteenths of the volume of 0.1M silver nitrate used in the second titration.

1 ml of 1M sodium hydroxide is equivalent to 0.1654 g of C2H3Cl3O2.

STORAGE

Store in an airtight container.

Glucose

C6H12O6,H2O 198.2

Preparations

Glucose Intravenous Infusion

Glucose Irrigation Solution

Oral Rehydration Salts

Potassium Chloride and Glucose Intravenous Infusion

Potassium Chloride, Sodium Chloride and Glucose Intravenous Infusion

Sodium Chloride and Glucose Intravenous Infusion

DEFINITION

Glucose monohydrate is the monohydrate of D-(+)-glucopyranose.

CHARACTERS

It has the characters described in the monograph Glucose, anhydrous (177).

IDENTIFICATION

It complies with the identification tests prescribed in the monograph Glucose, anhydrous (177).

TESTS

It complies with the tests prescribed in the monograph Glucose, anhydrous (177) with the following

modification:

Water (2.5.12). 7.0 per cent to 9.5 per cent, determined on 0.50 g by the semi-micro determination

of water.

Pyrogens (2.6.8). If intended for use in large-volume preparations for parenteral use, the competent

authority may require that it comply with the test for pyrogens carried out as follows. Inject per

kilogram of the rabbit’s mass 10 ml of a solution containing 55 mg per millilitre of the substance to

be examined in water for injections R.

STORAGE

Store in a well-closed container.

LABELLING

The label states where applicable, that the substance is apyrogenic.

Galactose

C6H12O16 180.2

DEFINITION

Galactose is D-galactopyranose.

CHARACTERS

A white, crystalline or finely granulated powder, freely soluble or soluble in water, very slightly

soluble in alcohol.

IDENTIFICATION

First identification: A.

Second identification: B, C.

A. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum

obtained with galactose CRS. Examine the substances prepared as discs.

B. Examine by thin-layer chromatography (2.2.27), using a suitable silica gel as the coating

substance.

Test solution. Dissolve 10 mg of the substance to be examined in a mixture of 2 volumes of water R

and 3 volumes of methanol R and dilute to 20 ml with the same mixture of solvents.

Reference solution (a). Dissolve 10 mg of galactose CRS in a mixture of 2 volumes of water R and 3 volumes of methanol R and dilute to 20 ml with the same mixture of solvents.

Reference solution (b). Dissolve 10 mg of galactose CRS, 10 mg of glucose CRS and 10 mg of lactose CRS in a mixture of 2 volumes of water R and 3 volumes of methanol R and dilute to 20 ml with the same mixture of solvents.

Apply to the plate 2 μl of each solution and thoroughly dry the starting points. Develop in an

unsaturated tank over a path of 15 cm using a mixture of 15 volumes of water R and 85 volumes of

propanol R. Dry the plate in a current of warm air. Spray uniformly with a solution of 0.5 g of

thymol R in a mixture of 5 ml of sulphuric acid R and 95 ml of alcohol R. Heat in an oven at 130ºC for 10 min. The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with reference solution (a). The test is not valid unless the chromatogram obtained with reference solution (b) shows three clearly separated spots.

C. Dissolve 0.1 g in 10 ml of water R. Add 3 ml of cupri-tartaric solution R and heat. An orange to red precipitate is formed.

TESTS

Solution S Dissolve with heating in a water-bath at 50ºC, 10.0 g in carbon dioxide-free water R

prepared from distilled water R and dilute to 50 ml with the same solvent.

Appearance of solution Solution S is clear (2.2.1) and not more intensely coloured than reference

solution B8 (Method II, 2.2.2).

Acidity or alkalinity To 30 ml of solution S add 0.3 ml of phenolphthalein solution R. The solution is colourless. Not more than 1.5 ml of 0.01M sodium hydroxide is required to change the colour of the indicator to pink.

Specific optical rotation (2.2.7). Dissolve 10.00 g in 80 ml of water R and add 0.2 ml of dilute

ammonia R1. Allow to stand for 30 min and dilute to 100.0 ml with water R. The specific optical

rotation is +78.0º to +81.5º, calculated with reference to the anhydrous substance.

Barium Dilute 5 ml of solution S to 10 ml with distilled water R. Add 1 ml of dilute sulphuric acid R. When examined immediately and after 1 h, any opalescence in the solution is not more intense than that in a mixture of 5 ml of solution S and 6 ml of distilled water R.

Lead (2.4.10). It complies with the limit test for lead in sugars (0.5 ppm).

Water (2.5.12). Not more than 1.0 per cent, determined on 1.00 g by the semi-micro determination

of water.

Sulphated ash To 5 ml of solution S add 2 ml of sulphuric acid R, evaporate to dryness on a waterbath and ignite to constant mass. The residue weighs not more than 1 mg (0.1 per cent).

Microbial contamination Total viable aerobic count (2.6.12) not more than 102 microorganisms

per gram.

STORAGE

Store in a well-closed container.

Lactose

C12H22O11,H2O 360.3

Action and use Pharmaceutical aid.

DEFINITION

Lactose monohydrate is the monohydrate of O-D-galactopyranosyl-(1,4)--D-glucopyranose. It

may be modified as to its physical characteristics and may contain varying proportions of amorphous lactose.

CHARACTERS

A white or almost white, crystalline powder, freely but slowly soluble in water, practically insoluble in alcohol.

IDENTIFICATION

First identification: A, D.

Second identification: B, C, D.

A. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum

obtained with lactose CRS.

B. Examine by thin-layer chromatography (2.2.27), using silica gel G R as the coating substance.

Test solution. Dissolve 10 mg of the substance to be examined in a mixture of 2 volumes of water R

and 3 volumes of methanol R and dilute to 20 ml with the same mixture of solvents.

Reference solution (a). Dissolve 10 mg of lactose CRS in a mixture of 2 volumes of water R and 3

volumes of methanol R and dilute to 20 ml with the same mixture of solvents.

Reference solution (b). Dissolve 10 mg each of fructose CRS, glucose CRS, lactose CRS and sucrose CRS in a mixture of 2 volumes of water R and 3 volumes of methanol R and dilute to 20 ml with the same mixture of solvents.

Apply separately to the plate 2 μl of each solution and thoroughly dry the starting points. Develop

over a path of 15 cm using a mixture of 10 volumes of water R, 15 volumes of methanol R, 25

volumes of anhydrous acetic acid R and 50 volumes of ethylene chloride R, measured accurately since a slight excess of water produces cloudiness. Dry the plate in a current of warm air. Repeat the

development immediately, after renewing the mobile phase. Dry the plate in a current of warm air

and spray evenly with a solution of 0.5 g of thymol R in a mixture of 5 ml of sulphuric acid R and

95 ml of alcohol R. Heat at 130°C for 10 min. The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with reference solution (a). The test is not valid unless the chromatogram obtained with reference solution (b) shows four clearly separated spots.

C. Dissolve 0.25 g in 5 ml of water R. Add 5 ml of ammonia R and heat in a water-bath at 80°C for

10 min. A red colour develops.

D. It complies with the test for water (see tests).

TESTS

Appearance of solution Dissolve 1.0 g in water R, heating to 50°C, dilute to 10 ml with the same

solvent and allow to cool. The solution is clear (2.2.1) and not more intensely coloured than

reference solution BY7 (Method II, 2.2.2).

Acidity or alkalinity Dissolve 6.0 g by boiling in 25 ml of carbon dioxide-free water R, cool and add 0.3 ml of phenolphthalein solution R. The solution is colourless. Not more than 0.4 ml of 0.1M sodium hydroxide is required to change the colour of the indicator to pink.

Specific optical rotation (2.2.7). Dissolve 10.0 g in 80 ml of water R, heating to 50°C. Allow to

cool and add 0.2 ml of dilute ammonia R1. Allow to stand for 30 min and dilute to 100.0 ml with

water R. The specific optical rotation is +54.4° to +55.9°, calculated with reference to the anhydrous substance.

Absorbance (2.2.25). Dissolve 1.0 g in boiling water R and dilute to 10.0 ml with the same solvent

(solution A). The absorbance of the solution measured at 400 nm is not greater than 0.04. Dilute

1.0 ml of solution A to 10.0 ml with water R. Examine the solution from 210 nm to 300 nm. At

wavelengths from 210 nm to 220 nm, the absorbance is not greater than 0.25. At wavelengths from

270 nm to 300 nm, the absorbance is not greater than 0.07.

Heavy metals (2.4.8). Dissolve 4.0 g in water R with warming, add 1 ml of 0.1M hydrochloric acid

and dilute to 20 ml with water R. 12 ml of the solution complies with limit test A for heavy metals

(5 ppm). Prepare the standard using lead standard solution (1 ppm Pb) R.

Water (2.5.12). 4.5 per cent to 5.5 per cent, determined on 0.50 g by the semi-micro determination

of water, using a mixture of 1 volume of formamide R and 2 volumes of methanol R as the solvent.

Sulphated ash Not more than 0.1 per cent. To 1.0 g add 1 ml of sulphuric acid R, evaporate to

dryness on a water-bath and ignite to constant mass.

Microbial contamination Total viable aerobic count (2.6.12) not more than 102 micro-organisms

per gram, determined by plate-count. It complies with the test for Escherichia coli (2.6.13).

STORAGE

Store in an airtight container.