Приложение 12 Частные фармакопейные статьи для лс галогенпроизводных углеводородов, спиртов, простых и сложных эфиров

(ЕР)

Ethyl Chloride

H3C CH2Cl

C2H5Cl 64.52

Definition Ethyl Chloride is chloroethane. It may be prepared by the action of hydrogen chloride

on Ethanol or on Industrial Methylated Spirit; in the latter case it may contain a small variable

proportion of methyl chloride.

Characteristics Gaseous at ambient temperatures and pressures, but usually compressed to a

colourless, mobile, flammable and very volatile liquid; odour, ethereal.

Slightly soluble in water; miscible with ethanol (96%) and with ether.

Identification

A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of ethyl chloride (RS 135).

B. Burns with a luminous flame with the production of an acid gas.

Acidity or alkalinity Shake 10 ml with 10 ml of iced water and allow the ethyl chloride to evaporate spontaneously. The residual liquid is neutral to litmus solution.

Ethanol Warm 5 ml of the residual liquid obtained in the test for Acidity or alkalinity with iodinated potassium iodide solution and sodium carbonate. No yellow crystals of iodoform are produced.

Ionisable chloride 5 ml of the residual liquid obtained in the test for Acidity or alkalinity yields no

turbidity with silver nitrate solution.

Distillation range Fit a dry 100-ml measuring cylinder with a stopper carrying a short exit tube not

less than 6 mm in internal diameter and an accurately standardised short-bulb thermometer covering

the range –20° to +30° and graduated in increments of 0.1°. Cover the bulb of the thermometer with

a piece of very fine muslin, free from grease and sizing materials, so that one end hangs down about

10 mm below the bulb. Cool the cylinder in ice, transfer to it 100 ml of the sample, previously cooled in ice, insert the stopper and adjust the thermometer so that the end of the muslin dips into the liquid and the bulb is above the surface. Replace the ice with water at 24° to 26° and observe the

temperature when 5 ml of sample has evaporated and again when 5 ml remains. Continually lower

the thermometer to maintain its position relative to the liquid surface throughout the test. Correct the observed temperature by adding 0.26° for every kPa that the barometric pressure is below 101.3 kPa or by subtracting 0.26° for every kPa above. The corrected temperature range is 12.0° to 12.5°.

Apparent specific gravity (0°/15°) Cool a sufficient quantity to about –5° by surrounding the

container with a mixture of methanol and solid carbon dioxide. Transfer the cooled substance being

examined to a hydrometer cylinder standing in melting ice and insert a hydrometer and a thermometer.

The reading on the hydrometer when the temperature has risen to 0° is 0.921 to 0.926.

Other organic compounds On evaporation, no foreign odour is detectable at any stage.

Non-volatile matter When evaporated and dried at 105°, leaves not more than 0.01% w/w of

residue.

Storage Ethyl Chloride should be protected from light and stored at a temperature not exceeding

20°.

Action and use Anaesthetic.

Halothane

C2HBrClF3 197.4

Action and use General anaesthetic.

DEFINITION

Halothane is (RS)-2-bromo-2-chloro-1,1,1-trifluoroethane to which 0.01 per cent m/m of thymol has

been added.

CHARACTERS

A clear, colourless, mobile, heavy, non-flammable liquid, slightly soluble in water, miscible with

ethanol, with ether and with trichloroethylene.

IDENTIFICATION

First identification: B.

Second identification: A, C.

A. It complies with the test for distillation range (see Tests).

B. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the Ph. Eur. Reference spectrum of halothane. Examine the substance in a 0.1 mm cell.

C. Add 0.1 ml of the substance to be examined to 2 ml of 2-methyl-2-propanol R in a test-tube. Add

1 ml of copper edetate solution R, 0.5 ml of concentrated ammonia R and a mixture of 0.4 ml of strong hydrogen peroxide solution R and 1.6 ml of water R (solution a). Prepare a blank at the same time (solution b). Place both tubes in a water-bath at 50°C for 15 min, cool and add 0.3 ml of glacial acetic acid R. To 1 ml of each of solutions (a) and (b) add 0.5 ml of a mixture of equal volumes of freshly prepared alizarin S solution R and zirconyl nitrate solution R. Solution (a) is yellow and solution (b) is red.

To 1 ml of each of solutions (a) and (b) add 1 ml of buffer solution pH 5.2 R, 1 ml of phenol red

solution R diluted 1 in 10 with water R and 0.1 ml of chloramine solution R. Solution (a) is bluish-violet and solution (b) is yellow.

To 2 ml of each of solutions (a) and (b) add 0.5 ml of a mixture of 25 volumes of sulphuric acid R and 75 volumes of water R, 0.5 ml of acetone R and 0.2 ml of a 50 g/l solution of potassium bromate R and shake. Warm the tubes in a water-bath at 50°C for 2 min, cool and add 0.5 ml of a mixture of equal volumes of nitric acid R and water R and 0.5 ml of silver nitrate solution R2. Solution (a) is opalescent and a white precipitate is formed after a few minutes; solution (b) remains clear.

TESTS

Acidity or alkalinity To 20 ml add 20 ml of carbon dioxide-free water R, shake for 3 min and allow to stand. Separate the aqueous layer and add 0.2 ml of bromocresol purple solution R. Not more than 0.1 ml of 0.01M sodium hydroxide or 0.6 ml of 0.01M hydrochloric acid is required to change the colour of the indicator.

Relative density (2.2.5). 1.872 to 1.877.

Distillation range (2.2.11). It distils completely between 49.0°C and 51.0°C, 95 per cent distilling

within a range of 1.0°C.

Volatile related substances Examine by gas chromatography (2.2.28), using trichlorotrifluoroethane

CRS as the internal standard.

Test solution (a). Use the substance to be examined.

Test solution (b). Dilute 5.0 ml of trichlorotrifluoroethane CRS to 100.0 ml with the substance to be

examined. Dilute 1.0 ml of the solution to 100.0 ml with the substance to be examined. Dilute

1.0 ml of this solution to 10.0 ml with the substance to be examined.

The chromatographic procedure may be carried out using:

— a column 2.75 m long and 5 mm in internal diameter packed with silanised diatomaceous earth for gas chromatography R1 (180 μm to 250 μm), the first 1.8 m being impregnated with 30 per cent

m/m of macrogol 400 R and the remainder with 30 per cent m/m of dinonyl phthalate R,

— nitrogen for chromatography R as the carrier gas at a flow rate of 30 ml/min,

— a flame-ionisation detector,

maintaining the temperature of the column at 50°C. Inject 5 μl of test solutions (a) and (b).

In the chromatogram obtained with test solution (b), the sum of the areas of the peaks, apart from the principal peak and the peak due to the internal standard, is not greater than the area of the peak due to the internal standard, corrected if necessary for any impurity with the same retention time as the internal standard (0.005 per cent).

Bromides and chlorides To 10 ml add 20 ml of water R and shake for 3 min. To 5 ml of the

aqueous layer add 5 ml of water R, 0.05 ml of nitric acid R and 0.2 ml of silver nitrate solution R1. The solution is not more opalescent than a mixture of 5 ml of the aqueous layer and 5 ml of water R.

Bromine and chlorine To 10 ml of the aqueous layer obtained in the test for bromides and

chlorides add 1 ml of potassium iodide and starch solution R. No blue colour is produced.

Thymol Examine by gas chromatography (2.2.28), using menthol R as the internal standard.

Internal standard solution. Dissolve 0.10 g of menthol R in methylene chloride R and dilute to 100.0 ml with the same solvent.

Test solution. To 20.0 ml of the substance to be examined add 5.0 ml of the internal standard

solution.

Reference solution. Dissolve 20.0 mg of thymol R in methylene chloride R and dilute to 100.0 ml with the same solvent. To 20.0 ml, add 5.0 ml of the internal standard solution.

The chromatographic procedure may be carried out using:

— a fused-silica capillary column 15 m long and 0.53 mm in internal diameter coated with a 1.5 μm

film of polydimethylsiloxane R,

— nitrogen for chromatography R as the carrier gas at a flow rate of 15 ml/min,

— a flame-ionisation detector,

maintaining the temperature of the column at 150°C and that of the injection port at 170°C and of

the detector at 200°C.

Inject separately 1.0 μl of the internal standard solution and of the test and reference solutions. In

the chromatogram obtained with the test solution, the area of the peak due to thymol is not less than

75 per cent and not more than 115 per cent of the area of the corresponding peak in the chromatogram obtained with the reference solution (0.008 per cent m/m to 0.012 per cent m/m).

Non-volatile matter Evaporate 50 ml to dryness on a water-bath and dry the residue in an oven at

100°C to 105°C for 2 h. The residue weighs not more than 1 mg (20 mg/l).

STORAGE

Store in an airtight container, protected from light, at a temperature not exceeding 25°C. The choice

of material for the container is made taking into account the particular reactivity of halothane with

certain metals

Ethanol

Absolute Alcohol; Dehydrated Alcohol

H3C CH2OH

C2H6O 46.07

DEFINITION

Anhydrous ethanol contains not less than 99.5 per cent V/V of C2H6O (99.2 per cent m/m), at 20°C.

CHARACTERS

A colourless, clear, volatile, flammable liquid, hygroscopic, miscible with water and with methylene chloride. It burns with a blue, smokeless flame.

It boils at 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. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the Ph. Eur. referencespectrum of anhydrous ethanol.

C. Mix 0.1 ml with 1 ml of a 10 g/l solution of potassium permanganate R and 0.2 ml of dilute sulphuricacid 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 min to 15 min.

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 0.05M iodine. A yellow precipitate is formed within 30 min.

TESTS

Appearance It is clear (2.2.1) and colourless (Method II, 2.2.2) when compared with water R. Dilute 1.0 ml to 20 ml with water R. After standing for 5 min, the dilution remains clear when compared with water R (2.2.1).

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 0.01M sodium hydroxide. The solution is pink (30 ppm, expressed as acetic acid).

Relative density (2.2.5). 0.7907 to 0.7932.

Absorbance Examined between 235 nm and 340 nm, the absorbance (2.2.25) measured in a 5 cm

cell using water R as the compensation liquid is not greater than 0.40 at 240 nm, 0.30 between

250 nm and 260 nm, and 0.10 between 270 nm and 340 nm. The absorption curve is smooth.

Volatile impurities Examine by gas chromatography (2.2.28).

Test solution (a). The substance to be examined.

Test solution (b). Add 150 μl of 4-methylpentan-2-ol R to 500.0 ml of the substance to be examined.

Reference solution (a). Dilute 100 μl of anhydrous methanol R to 50.0 ml with the substance to be

examined. Dilute 5.0 ml of the solution to 50.0 ml with the substance to be examined.

Reference solution (b). Dilute 50 μl of anhydrous methanol R and 50 μl of acetaldehyde R to 50.0 ml with the substance to be examined. Dilute 100 μl of the solution to 10.0 ml with the substance to be examined.

Reference solution (c). Dilute 150 μl of acetal R to 50.0 ml with the substance to be examined. Dilute 100 μl of the solution to 10.0 ml with the substance to be examined.

Reference solution (d). Dilute 100 μl of benzene R to 100.0 ml with the substance to be examined.

Dilute 100 μl of the solution to 50.0 ml with the substance to be examined.

The chromatographic procedure may be carried out using:

— a fused-silica capillary column 30 m long and 0.32 mm in internal diameter coated with

poly[(cyanopropyl)(phenyl)][dimethyl]siloxane R (film thickness 1.8 μm),

— helium for chromatography R as the carrier gas at a column flow rate of 1.5 ml/min,

— a flame-ionisation detector,

Inject 1 μl of reference solution (b). Adjust the sensitivity of the system so that the heights of the

two peaks eluting before the principal peak, are at least 50 per cent of the full-scale of the recorder.

The test is not valid unless in the chromatogram obtained, the resolution between the first peak

(acetaldehyde) and the second peak (methanol) is at least 2.0. If necessary, decrease the initial

column temperature.

Inject 1 μl of each solution. The area of any peak corresponding to methanol in the chromatogram

obtained with test solution (a) is not greater than half the area of the corresponding peak in the

chromatogram obtained with reference solution (a) (200 ppm V/V).

Calculate the sum of the contents (ppm) of acetaldehyde and acetal from the areas of the corresponding peaks in the chromatogram obtained with test solution (a) using the following expression:

AE=area of the acetaldehyde peak in the chromatogram obtained with test solution (a),

AT=area of the acetaldehyde peak in the chromatogram obtained with reference solution (b),

CE=area of the acetal peak in the chromatogram obtained with test solution (a),

CT=area of the acetal peak in the chromatogram obtained with reference solution (c).

The sum of the contents of acetaldehyde and acetal is not greater than 10 ppm (V/V), expressed as

acetaldehyde.

Calculate the content of benzene (ppm) from the area of the corresponding peak in the chromatogram

obtained with test solution (a) using the following expression:

BE=area of the benzene peak in the chromatogram obtained with test solution (a),

BT=area of the benzene peak in the chromatogram obtained with reference solution (d).

If necessary, the identity of benzene can be confirmed using another suitable chromatographic

system (stationary phase with a different polarity).

It contains not more than 2 ppm (V/V) of benzene.

In the chromatogram obtained with test solution (b), the sum of the areas of any peaks, apart from

the principal peak and any peak due to methanol, acetaldehyde, acetal or benzene, is not greater than the area of the peak corresponding to 4-methylpentan-2-ol (300 ppm). Disregard any peak with an area less than 0.03 times that of the peak corresponding to 4-methylpentan-2-ol in the chromatogram obtained with test solution (b).

Residue on evaporation Evaporate 100 ml to dryness on a water-bath and dry at 100°C to 105°C

for 1 h. The residue weighs not more than 2.5 mg (25 ppm m/V).

STORAGE

Store in a well-closed container, protected from light.

Glycerol

Glycerin

C3H8O3 92.1

Action and use Lubricant; laxative.

Preparation

Glycerol Suppositories

DEFINITION

Glycerol contains not less than 98.0 per cent and not more than the equivalent of 101.0 per cent of

propane-1,2,3-triol, calculated with reference to the anhydrous substance.

CHARACTERS

A syrupy liquid, unctuous to the touch, colourless or almost colourless, clear, very hygroscopic,

miscible with water and with alcohol, slightly soluble in acetone, practically insoluble in ether, in fatty oils and in essential oils.

IDENTIFICATION

First identification: A, B.

Second identification: A, C, D.

A. It complies with the test for refractive index (see Tests).

B. To 5 ml add 1 ml of water R and mix carefully. Examine the solution by infrared absorption

spectrophotometry (2.2.24), comparing with the Ph. Eur. reference spectrum of glycerol (85 per cent).

C. Mix 1 ml with 0.5 ml of nitric acid R. Superimpose 0.5 ml of potassium dichromate solution R. A blue ring develops at the interface of the liquids. Within 10 min, the blue colour does not diffuse into the lower layer.

D. Heat 1 ml with 2 g of potassium hydrogen sulphate R in an evaporating dish. Vapours (acrolein) are volved which blacken filter paper impregnated with alkaline potassium tetraiodomercurate solution R.

TESTS

Solution S Dilute 100.0 g to 200.0 ml with carbon dioxide-free water R.

Appearance of solution Solution S is clear (2.2.1). Dilute 10 ml of solution S to 25 ml with

water R. The solution is colourless (Method II, 2.2.2).

Acidity or alkalinity To 50 ml of solution S add 0.5 ml of phenolphthalein solution R. The solution is colourless. Not more than 0.2 ml of 0.1M sodium hydroxide is required to change the colour of the indicator to pink.

Refractive index (2.2.6). 1.470 to 1.475.

Aldehydes Place 7.5 ml of solution S in a ground-glass-stoppered flask and add 7.5 ml of water R

and 1.0 ml of decolorised pararosaniline solution R. Close the flask and allow to stand for 1 h at a

temperature of 25 ± 1°C. The absorbance of the solution measured at 552 nm (2.2.25) is not greater

than that of a standard prepared at the same time and in the same manner using 7.5 ml of

formaldehyde standard solution (5 ppm CH2O) R and 7.5 ml of water R. The test is not valid unless the standard is pink.

Esters Add 0.1M sodium hydroxide to the final solution obtained in the test for acidity or alkalinity

until a total of 10.0 ml has been added. Boil under a reflux condenser for 5 min. Cool. Add 0.5 ml of phenolphthalein solution R and titrate with 0.1M hydrochloric acid. Not less than 8.0 ml of 0.1M hydrochloric acid is required to change the colour of the indicator.

Impurity A and related substances Examine by gas chromatography (2.2.28).

Test solution. Dilute 10.0 ml of solution S to 100.0 ml with water R.

Reference solution (a). Dissolve 1.000 g of diethylene glycol R in water R and dilute to 100.0 ml with the same solvent.

Reference solution (b). Dilute 1.0 ml of reference solution (a) to 10.0 ml with the test solution. Dilute 1.0 ml of this solution to 20.0 ml with the test solution.

Reference solution (c). Mix 1.0 ml of the test solution and 5.0 ml of reference solution (a) and dilute

to 100.0 ml with water R. Dilute 1.0 ml of this solution to 10.0 ml with water R.

Reference solution (d). Dilute 5.0 ml of reference solution (a) to 100.0 ml with water R.

The chromatographic procedure may be carried out using:

— a fused-silica column 30 m long and 0.53 mm in internal diameter coated with a mixture of

cross-linked polycyanopropylphenylsiloxane (6 per cent) and polydimethylsiloxane (94 per cent)

(film thickness 3 μm),

— helium for chromatography R as the carrier gas at a linear velocity of about 38 cm/s and with a split ratio of about 10:1,

— a flame-ionisation detector,

maintaining the temperature of the column at 100°C until injection, then raising the temperature at a

rate of 7.5°C per minute to 220°C and maintaining at 220°C for 4 min; maintaining the temperature

of the injection port at 220°C and that of the detector at 250°C.

Inject 0.5 μl of the reference solution (c). Adjust the sensitivity of the system such that the height of

the peak due to impurity A is at least 50 per cent of the full scale of the recorder. When the chromatograms are recorded in the prescribed conditions, the substances are eluted in the following order: impurity A and glycerol.

The test is not valid unless: in the chromatogram obtained with reference solution (c), the

resolution between the peaks corresponding to impurity A and to glycerol is at least 7.0.

Inject 0.5 μl of the test solution, 0.5 μl of reference solution (b) and 0.5 μl of reference solution (d).

In the chromatogram obtained with the test solution: the area of any peak corresponding to impurity

A is not greater than half the area of the corresponding peak in the chromatogram obtained with

reference solution (b) (0.1 per cent); the area of any peak, apart from the peak corresponding to

impurity A, and with a retention time less than the retention time of glycerol, is not greater than half

the area of the peak corresponding to impurity A in the chromatogram obtained with reference

solution (b) (0.1 per cent); the sum of the areas of any peaks with retention times greater than the

retention time of glycerol, is not greater than 2.5 times the area of the peak corresponding to impurity

A in the chromatogram obtained with reference solution (b) (0.5 per cent). Disregard any peak with

an area less than 0.05 times the area of the peak corresponding to impurity A in the chromatogram

obtained with reference solution (d).

Halogenated compounds To 10 ml of solution S add 1 ml of dilute sodium hydroxide solution R,

5 ml of water R and 50 mg of halogen-free nickel-aluminium alloy R. Heat on a water-bath for 10 min, allow to cool and filter. Rinse the flask and the filter with water R until 25 ml of filtrate is obtained.

To 5 ml of the filtrate add 4 ml of alcohol R, 2.5 ml of water R, 0.5 ml of nitric acid R and 0.05 ml of silver nitrate solution R2 and mix. Allow to stand for 2 min. Any opalescence in the solution is not more intense than that in a standard prepared at the same time by mixing 7.0 ml of chloride standard solution (5 ppm Cl) R, 4 ml of alcohol R, 0.5 ml of water R, 0.5 ml of nitric acid R and 0.05 ml of silver nitrate solution R2 (35 ppm).

Sugars To 10 ml of solution S add 1 ml of dilute sulphuric acid R and heat on a water-bath for 5 min. Add 3 ml of carbonate-free dilute sodium hydroxide solution R (prepared by the method described for carbonate-free 1M sodium hydroxide (4.2.2), mix and add dropwise 1 ml of freshly prepared copper sulphate solution R. The solution is clear and blue. Continue heating on the water-bath for 5 min. The solution remains blue and no precipitate is formed.

Chlorides (2.4.4). 1 ml of solution S diluted to 15 ml with water R complies with the limit test for

chlorides (10 ppm). Prepare the standard using 1 ml of chloride standard solution (5 ppm Cl) R diluted to 15 ml with water R.

Heavy metals (2.4.8). Dilute 8 ml of solution S 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). Not more than 2.0 per cent, determined on 1.500 g by the semi-micro determination of water.

Sulphated ash (2.4.14). Not more than 0.01 per cent, determined on 5.0 g after heating to boiling

and ignition.

ASSAY

Thoroughly mix 0.1000 g with 45 ml of water R. Add 25.0 ml of a 21.4 g/l solution of

sodium periodate R. Allow to stand protected from light for 15 min. Add 5.0 ml of a 500 g/l solution of ethylene glycol R and allow to stand protected from light for 20 min. Using 0.5 ml of phenolphthalein solution R as indicator, titrate with 0.1M sodium hydroxide. Carry out a blank titration. 1 ml of 0.1M sodium hydroxide is equivalent to 9.21 mg of C3H8O3.

STORAGE

Store in an airtight container.

Ether

H3C O CH3

C4H10O 74.1

When solvent ether is demanded, Ether shall be supplied.

DEFINITION

Ether is diethyl ether which may contain a suitable non-volatile antioxidant at a suitable concentration.

CHARACTERS

A clear, colourless liquid, volatile, highly flammable, soluble in water, miscible with alcohol, with

methylene chloride and with fatty oils.

IDENTIFICATION

A. It complies with the test for relative density (see Tests).

B. It complies with the test for distillation range (see Tests).

TESTS

Acidity To 20 ml of alcohol R add 0.25 ml of bromothymol blue solution R1 and, dropwise, 0.02M

sodium hydroxide until a blue colour persists for 30 s. Add 25 ml of the substance to be examined,

shake and add, dropwise, 0.02M sodium hydroxide until the blue colour reappears and persists for 30 s.

Not more than 0.4 ml of 0.02M sodium hydroxide is required.

Relative density (2.2.5): 0.714 to 0.716.

Distillation range (2.2.11). Do not distil if the substance to be examined does not comply with the test for peroxides. It distils completely between 34.0°C and 35.0°C. Carry out the test using a suitable heating device and taking care to avoid directly heating the flask above the level of the liquid.

Non-volatile matter After ensuring that the substance to be examined complies with the test for peroxides, evaporate 50 ml to dryness on a water-bath and dry the residue in an oven at 100°C to 105°C. The residue weighs not more than 1 mg (20 mg/l).

Substances with a foreign odour Moisten a disc of filter paper 80 mm in diameter with 5 ml of the

substance to be examined and allow to evaporate. No foreign odour is perceptible immediately after

the evaporation.

Aldehydes To 10.0 ml in a ground-glass-stoppered cylinder add 1 ml of alkaline potassium

tetraiodomercurate solution R and shake for 10 s. Allow to stand for 5 min, protected from light. The lower layer may show yellow or reddish-brown opalescence but not grey or black opalescence.

Peroxides Place 8 ml of potassium iodide and starch solution R in a 12 ml ground-glass-stoppered

cylinder about 15 mm in diameter. Fill completely with the substance to be examined, mix and allow to stand protected from light for 5 min. No colour develops.

Water (2.5.12). Not more than 2 g/l, determined on 20 ml by the semi-micro determination of

water.

STORAGE

Store in an airtight container, protected from light, at a temperature of 8°C to 15°C.

LABELLING

The label states, where appropriate, the name and concentration of any added non-volatile

antioxidant.

Anaesthetic Ether

C4H10O 74.1

DEFINITION

Anaesthetic ether is diethyl ether which may contain a suitable non-volatile antioxidant at an

appropriate concentration.

CHARACTERS

A clear, colourless liquid, volatile, very mobile, highly flammable, soluble in 15 parts of water,

miscible with alcohol and with fatty oils.

IDENTIFICATION

A. It complies with the test for relative density (see Tests).

B. It complies with the test for distillation range (see Tests).

TESTS

Relative density (2.2.5): 0.714 to 0.716.

Distillation range (2.2.11). Do not distil if the substance to be examined does not comply with the test for peroxides. It distils completely between 34.0°C and 35.0°C. Carry out the test using a suitable heating device and taking care to avoid directly heating the flask above the level of the liquid.

Non-volatile matter After ensuring that the substance to be examined complies with the test for peroxides, evaporate 50 ml to dryness on a water-bath and dry the residue at 100°C to 105°C. The residue weighs not more than 1 mg (20 mg/l).

Substances with a foreign odour Moisten a disc of filter paper 80 mm in diameter with 5 ml of the

substance to be examined and allow to evaporate. No foreign odour is perceptible immediately after

the evaporation.

Acids To 20 ml of alcohol R add 0.25 ml of bromothymol blue solution R1 and, dropwise, 0.02M sodium hydroxide until a blue colour persists for 30 s. Add 25 ml of the substance to be examined, shake and add, dropwise, 0.02M sodium hydroxide until the blue colour reappears and persists for 30 s. Not more than 0.4 ml of 0.02M sodium hydroxide is required.

Acetone and aldehydes To 10.0 ml in a ground-glass-stoppered cylinder add 1 ml of alkaline

potassium tetra-iodomercurate solution R and shake for 10 s. Allow to stand for 5 min, protected from light. The lower layer shows only a slight opalescence.

If the substance to be examined does not comply with the test, distil 40 ml, after ensuring that the

substance to be examined complies with the test for peroxides, until only 5 ml remains. Collect the distillate in a receiver cooled by placing in a bath of iced water and repeat the test described above using 10.0 ml of the distillate.

Peroxides Place 8 ml of potassium iodide and starch solution R in a 12 ml ground-glass-stoppered

cylinder about 15 mm in diameter. Fill completely with the substance to be examined, shake

vigorously and allow to stand protected from light for 30 min. No colour is produced.

Water (2.5.12). Not more than 2 g/l, determined on 20 ml by the semi-micro determination of

water.

STORAGE

Store in an airtight container, protected from light, at a temperature of 8°C to 15°C. The contents of

a partly filled container may deteriorate rapidly.

LABELLING

The label states, where appropriate, the name and concentration of any added non-volatile

antioxidant.