EUROPEAN PHARMACOPOEIA 5.

Optical rotation (2.2.7). Dissolve 2.50 g in water R and

dilute to 25.0 ml with the same solvent. The angle of optical
rotation, measured in a 2 dm tube, is 0.25 to + 0.05.
Related substances. Examine by thin-layer chromatography
(2.2.27), using a TLC silica gel G plate R.
Test solution. Dissolve 0.2 g of the substance to be examined
in a mixture of 1 volume of water R and 9 volumes of
methanol R and dilute to 5 ml with the same mixture of
solvents.
Reference solution. Dilute 0.5 ml of the test solution to
100 ml with a mixture of 1 volume of water R and 9 volumes
of methanol R.
Apply to the plate 5 l of each solution. Develop over a path
of 15 cm using a mixture of 10 volumes of methanol R,
15 volumes of anhydrous formic acid R, 15 volumes of
water R and 60 volumes of ethyl acetate R. Dry the plate at
100 C to 105 C until the solvent has evaporated, allow
to cool and spray with dilute potassium iodobismuthate
solution R until the spots appear. Any spot in the
chromatogram obtained with the test solution, apart from
the principal spot, is not more intense than the spot in the
chromatogram obtained with the reference solution (0.5 per
cent).
Apomethylatropine. Dissolve 0.10 g in 0.01 M hydrochloric
acid and dilute to 100.0 ml with the same acid. Measure the
absorbances (2.2.25) at the maxima at 252 nm and 257 nm.
The ratio of the absorbance at 257 nm to that at 252 nm is
at least 1.19.
Loss on drying (2.2.32). Not more than 0.5 per cent,
determined on 0.500 g by drying in an oven at 100 C to
105 C.
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on the residue obtained in the test for loss on
drying.

Methylatropine nitrate

CHARACTERS
A white, crystalline powder or colourless crystals, freely
soluble in water, soluble in alcohol.
It melts at about 167 C.
IDENTIFICATION
First identification : B, E.
Second identification : A, C, D, E.
A. It complies with the test for optical rotation (see Tests).
B. Examine by infrared absorption spectrophotometry
(2.2.24), comparing with the spectrum obtained with
methylatropine nitrate CRS.
C. To a mixture of 2.5 ml of solution S (see Tests) and
2.5 ml of water R add 2 ml of dilute sodium hydroxide
solution R. No precipitate is formed.
D. To about 1 mg add 0.2 ml of fuming nitric acid R and
evaporate to dryness on a water-bath. Dissolve the
residue in 2 ml of acetone R and add 0.25 ml of a 30 g/l
solution of potassium hydroxide R in methanol R. A
violet colour develops.
E. To 0.05 ml of diphenylamine solution R add 0.05 ml of
a 1 in 10 dilution of solution S. An intense blue colour
is produced.

TESTS
Solution S. Dissolve 1.25 g in carbon dioxide-free water R
and dilute to 25 ml with the same solvent.
Appearance of solution. Solution S is clear (2.2.1) and not
more intensely coloured than reference solution B9 (2.2.2,
Method II).
Acidity or alkalinity. To 10 ml of solution S add 0.1 ml of
phenolphthalein solution R ; the solution is colourless. Add
0.5 ml of 0.01 M sodium hydroxide ; the solution is red.
Optical rotation (2.2.7). Dissolve 2.50 g in water R and
ASSAY
dilute to 25.0 ml with the same solvent. The angle of optical
Dissolve 0.300 g in 50 ml of anhydrous acetic acid R,
rotation, measured in a 2 dm tube, is 0.25 to + 0.05.
warming slightly if necessary. Titrate with 0.1 M perchloric
acid, determining the end-point potentiometrically (2.2.20). Related substances. Examine by thin-layer chromatography
(2.2.27), using silica gel G R as the coating substance.
1 ml of 0.1 M perchloric acid is equivalent to 38.43 mg of
Test solution. Dissolve 0.2 g of the substance to be examined
C18H26BrNO3.
in a mixture of 1 volume of water R and 9 volumes of
STORAGE
methanol R and dilute to 5 ml with the same mixture of
Store protected from light.
solvents.
Reference solution. Dilute 0.5 ml of the test solution to
01/2005:0512 100 ml with a mixture of 1 volume of water R and 9 volumes
of methanol R.
Apply to the plate 5 l of each solution. Develop over a path
METHYLATROPINE NITRATE
of 15 cm using a mixture of 10 volumes of methanol R,
15 volumes of anhydrous formic acid R, 15 volumes of
Methylatropini nitras
water R and 60 volumes of ethyl acetate R. Dry the plate at
100 C to 105 C until the solvent has evaporated, allow
to cool and spray with dilute potassium iodobismuthate
solution R until the spots appear. Any spot in the
chromatogram obtained with the test solution, apart from
the principal spot, is not more intense than the spot in the
chromatogram obtained with the reference solution (0.5 per
cent).
C18H26N2O6
Mr 366.4 Apomethylatropine. Dissolve 0.10 g in 0.01 M hydrochloric
acid and dilute to 100.0 ml with the same acid. Measure the
absorbances (2.2.25) at the maxima at 252 nm and 257 nm.
DEFINITION
The ratio of the absorbance at 257 nm to that at 252 nm is
Methylatropine nitrate contains not less than 99.0 per
not less than 1.17.
cent and not more than the equivalent of 101.0 per cent of
Halides. 15 ml of solution S complies with the limit test
(1R,3r,5S)-3-[[(2RS)-3-hydroxy-2-phenylpropanoyl]oxy]-8,8for chlorides (2.4.4). Prepare the standard using 1.5 ml of
dimethyl-8-azoniabicyclo[3.2.1]octane nitrate, calculated
chloride standard solution (5 ppm Cl) R (10 ppm).
with reference to the dried substance.
General Notices (1) apply to all monographs and other texts

2015

Methylcellulose

EUROPEAN PHARMACOPOEIA 5.0

Silver. Dissolve 1.0 g in 10 ml of water R and add 0.1 ml

of sodium sulphide solution R. Allow to stand for 2 min.
The solution is not more intensely coloured than reference
solution B8 (2.2.2, Method II) (10 ppm).
Loss on drying (2.2.32). Not more than 0.5 per cent,
determined on 0.500 g by drying in an oven at 100 C to
105 C.
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on the residue obtained in the test for loss on
drying.
ASSAY
Dissolve 0.300 g in 50 ml of anhydrous acetic acid R.
Titrate with 0.1 M perchloric acid determining the end-point
potentiometrically (2.2.20).
1 ml of 0.1 M perchloric acid is equivalent to 36.64 mg of
C18H26N2O6.
STORAGE
Store protected from light.
01/2005:0345

METHYLCELLULOSE
Methylcellulosum
DEFINITION
Methylcellulose is a partly O-methylated cellulose.
CHARACTERS
A white, yellowish-white or greyish-white powder or granules,
hygroscopic after drying, practically insoluble in hot water,
in acetone, in ethanol and in toluene. It dissolves in cold
water giving a colloidal solution.
IDENTIFICATION
A. Heat 10 ml of solution S (see Tests) in a water-bath while
stirring. At a temperature above 50 C the solution
becomes cloudy or a flocculent precipitate is formed. The
solution becomes clear again on cooling.
B. To 10 ml of solution S add 0.3 ml of dilute acetic acid R
and 2.5 ml of a 100 g/l solution of tannic acid R. A
yellowish-white, flocculent precipitate is formed which
dissolves in dilute ammonia R1.
C. In a test-tube about 160 mm long, thoroughly mix 1 g
with 2 g of finely powdered manganese sulphate R.
Introduce to a depth of 2 cm into the upper part of the
tube a strip of filter paper impregnated with a freshly
prepared mixture of l volume of a 20 per cent V/V solution
of diethanolamine R and 11 volumes of a 50 g/l solution
of sodium nitroprusside R, adjusted to about pH 9.8
with 1 M hydrochloric acid. Insert the tube 8 cm into a
silicone-oil bath at 190 C to 200 C. The filter paper does
not become blue within 10 min. Carry out a blank test.
D. Dissolve 0.2 g completely, without heating, in 15 ml of a
70 per cent m/m solution of sulphuric acid R. Pour the
solution with stirring into 100 ml of iced water R and
dilute to 250 ml with iced water R. In a test-tube, mix
thoroughly while cooling in iced water l ml of the solution
with 8 ml of sulphuric acid R, added dropwise. Heat in a
water-bath for exactly 3 min and immediately cool in iced
water. While the mixture is cold, carefully add 0.6 ml of
ninhydrin solution R2 and mix well. Allow to stand at
25 C. A pink colour is produced immediately and does
not become violet within 100 min.
2016

E. Place l ml of solution S on a glass plate. After evaporation

of the water a thin film is formed.
F. 0.2 g does not dissolve in 10 ml of toluene R nor in 10 ml
of ethanol R.
TESTS
Solution S. While stirring, introduce a quantity of the
substance to be examined equivalent to l.0 g of the dried
substance into 50 g of carbon dioxide-free water R heated to
90 C. Allow to cool, adjust the mass of the solution to 100 g
with carbon dioxide-free water R and stir until dissolution
is complete. Allow to stand at 2 C to 8 C for 1 h before
carrying out the test for appearance of solution.
Appearance of solution. Solution S is not more opalescent
than reference suspension III (2.2.1) and not more intensely
coloured than reference solution Y6 (2.2.2, Method II).
pH (2.2.3). The pH of solution S is 5.5 to 8.0.
Apparent viscosity. While stirring, introduce a quantity of
the substance to be examined equivalent to 6.00 g of the
dried substance into 150 g of water R heated to 90 C. Stir
with a propeller-type stirrer for 10 min, place the flask in
a bath of iced water, continue the stirring, and allow to
remain in the bath of iced water for 40 min to ensure that
dissolution is complete. Adjust the mass of the solution to
300 g, and centrifuge the solution to expel any entrapped
air. Adjust the temperature of the solution to 20 0.1 C.
Determine the viscosity (2.2.10) with a rotating viscometer
at 20 C and a shear rate of 10 s 1. The apparent viscosity is
not less than 75 per cent and not more than 140 per cent of
the value stated on the label.
Chlorides (2.4.4). 1 ml of solution S diluted to 15 ml with
water R complies with the limit test for chlorides (0.5 per
cent).
Heavy metals (2.4.8). 1.0 g complies with limit test C for
heavy metals (20 ppm). Prepare the standard using 2 ml of
lead standard solution (10 ppm Pb) R.
Loss on drying (2.2.32). Not more than 10.0 per cent,
determined on 1.000 g by drying in an oven at 100 C to
105 C.
Sulphated ash (2.4.14). Not more than 1.0 per cent,
determined on 1.000 g.
LABELLING
The label states the apparent viscosity in millipascal seconds
for a 2 per cent m/m solution.
01/2005:0045

METHYLDOPA
Methyldopum

C10H13NO4,11/2H2O

Mr 238.2

DEFINITION
Methyldopa contains not less than 98.5 per cent and
not more than the equivalent of 101.0 per cent of
(2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid,
calculated with reference to the anhydrous substance.

See the information section on general monographs (cover pages)