Oxygen

EUROPEAN PHARMACOPOEIA 5.0

as detector a spectrophotometer set at 210 nm.

Inject 10 l of reference solution (a). When the
chromatograms are recorded in the prescribed conditions the
retention times are : oxybutynin hydrochloride about 15 min
and impurity A about 24 min. Adjust the sensitivity of the
system so that the heights of the peaks in the chromatogram
obtained are about 20 per cent of the full scale of the
recorder. The test is not valid unless the resolution between
the peaks due to oxybutynin hydrochloride and to impurity A
is at least 11.0.
Inject 10 l of the test solution, 10 l of reference
solution (a) and 10 l of reference solution (b). Continue
the chromatography for about twice the retention time of
the principal peak. In the chromatogram obtained with the
test solution : the area of any peak due to impurity A is not
greater than 1.5 times the area of the peak due to impurity A
in the chromatogram obtained with reference solution (a)
(1.5 per cent) ; the sum of the areas of all the peaks, apart
from the principal peak and the peak due to impurity A,
is not greater than the area of the principal peak 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 principal peak in the chromatogram obtained
with reference solution (b).
Heavy metals (2.4.8). 12 ml of solution S complies with limit
test A 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 3.0 per cent
determined on 1.000 g by drying in an oven at 100-105 C.
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on 1.0 g.
ASSAY
Dissolve 0.300 g in a mixture of 5.0 ml of 0.01 M hydrochloric
acid and 50 ml of alcohol R. Carry out a potentiometric
titration (2.2.20), using 0.1 M sodium hydroxide. Read
the volume added between the two points of inflexion.
1 ml of 0.1 M sodium hydroxide is equivalent to 39.4 mg
of C22H32ClNO3.
STORAGE
Store protected from light.
IMPURITIES

A. 4-(diethylamino)but-2-ynyl (RS)-2-(cyclohex-3-enyl)-2cyclohexyl-2-hydroxyacetate,

B. 4-(diethylamino)but-2-ynyl 2-hydroxy-2,2-diphenylacetate
(diphenyl analogue of oxybutynin),
General Notices (1) apply to all monographs and other texts

C. R = CH3 : 4-(ethylmethylamino)but-2-ynyl
(RS)-2-cyclohexyl-2-hydroxy-2-phenylacetate
(methylethyl analogue of oxybutynin),
E. R = CH2-CH2-CH3 : 4-(ethylpropylamino)but-2-ynyl
(RS)-2-cyclohexyl-2-hydroxy-2-phenylacetate (ethylpropyl
analogue of oxybutynin),

D. (RS)-2-cyclohexyl-2-hydroxy-2-phenylacetic acid
(phenylcyclohexylglycolic acid).
01/2005:0417

OXYGEN
Oxygenium
O2

Mr 32.00

DEFINITION
Oxygen contains not less than 99.5 per cent V/V of O2.
This monograph applies to oxygen for medicinal use.
CHARACTERS
A colourless, odourless gas. At 20 C and at a pressure of
101 kPa, 1 volume dissolves in about 32 volumes of water.
PRODUCTION
Carbon dioxide. Not more than 300 ppm V/V, determined
using an infrared analyser (2.5.24).
Gas to be examined. The substance to be examined. It must
be filtered to avoid stray light phenomena.
Reference gas (a). Use oxygen R.
Reference gas (b). Use a mixture containing 300 ppm V/V
of carbon dioxide R1 in nitrogen R1.
Calibrate the apparatus and set the sensitivity using
reference gases (a) and (b). Measure the content of carbon
dioxide in the gas to be examined.
Carbon monoxide. Not more than 5 ppm V/V, determined
using an infrared analyser (2.5.25).
Gas to be examined. The substance to be examined. It must
be filtered to avoid stray light phenomena.
Reference gas (a). Use oxygen R.
Reference gas (b). Use a mixture containing 5 ppm V/V of
carbon monoxide R in nitrogen R1.
Calibrate the apparatus and set the sensitivity using
reference gases (a) and (b). Measure the content of carbon
monoxide in the gas to be examined.
Water. Not more than 67 ppm V/V, determined using an
electrolytic hygrometer (2.5.28).
Assay. Determine the concentration of oxygen using a
paramagnetic analyser (2.5.27).
2169

Oxymetazoline hydrochloride

EUROPEAN PHARMACOPOEIA 5.0

IDENTIFICATION
First identification : C.
Second identification : A, B.
A. Place a glowing splinter of wood in the substance to be
examined. The splinter bursts into flame.
B. Shake with alkaline pyrogallol solution R. The substance
to be examined is absorbed and the solution becomes
dark brown.
C. It complies with the limits of the assay.
TESTS
Carbon dioxide. Not more than 300 ppm V/V, determined
using a carbon dioxide detector tube (2.1.6).
Carbon monoxide. Not more than 5 ppm V/V, determined
using a carbon monoxide detector tube (2.1.6).
Water vapour. Not more than 67 ppm V/V, determined
using a water vapour detector tube (2.1.6).
STORAGE
Store as a compressed gas or liquid in appropriate containers,
complying with the legal regulations. Taps and valves are
not to be greased or oiled.
IMPURITIES
A. carbon dioxide,
B. carbon monoxide,
C. water.
01/2005:0943

OXYMETAZOLINE HYDROCHLORIDE
Oxymetazolini hydrochloridum

C16H25ClN2O

Mr 296.8

DEFINITION
Oxymetazoline hydrochloride contains not less than 99.0 per
cent and not more than the equivalent of 101.0 per cent of
3-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)2,4-dimethylphenol hydrochloride, calculated with reference
to the dried substance.
CHARACTERS
A white or almost white, crystalline powder, freely soluble in
water and 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
oxymetazoline hydrochloride CRS.
B. Examine the chromatograms obtained in the test
for related substances. The principal spot in the
chromatogram obtained with test solution (b) is similar
in position, colour and size to the principal spot in the
chromatogram obtained with reference solution (a).
2170

C. To a solution of about 2 mg in 1 ml of water R add 0.2 ml

of a 50 g/l solution of sodium nitroprusside R and 0.2 ml
of dilute sodium hydroxide solution R. Allow to stand
for 10 min. Add 2 ml of sodium hydrogen carbonate
solution R. A violet colour develops.
D. It gives reaction (a) of chlorides (2.3.1).
TESTS
Solution S. Dissolve 2.5 g in 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 BY7 (2.2.2,
Method II)
Acidity or alkalinity. Dissolve 0.25 g in water R and dilute
to 25 ml with the same solvent. Add 0.1 ml of methyl red
solution R and 0.2 ml of 0.01 M hydrochloric acid. The
solution is red. Not more than 0.4 ml of 0.01 M sodium
hydroxide is required to change the colour of the indicator
to yellow.
Related substances. Examine by thin-layer chromatography
(2.2.27), using silica gel G R as the coating substance.
Test solution (a). Dissolve 0.40 g of the substance to be
examined in a mixture of equal volumes of ethyl acetate R
and methanol R and dilute to 10 ml with the same mixture
of solvents.
Test solution (b). Dilute 1 ml of test solution (a) to 10 ml
with a mixture of equal volumes of ethyl acetate R and
methanol R.
Reference solution (a). Dissolve 40 mg of oxymetazoline
hydrochloride CRS in a mixture of equal volumes of ethyl
acetate R and methanol R and dilute to 10 ml with the same
mixture of solvents.
Reference solution (b). Dilute 1 ml of test solution (b) to
20 ml with a mixture of equal volumes of ethyl acetate R
and methanol R.
Reference solution (c). Dilute 1 ml of test solution (b) to
40 ml with a mixture of equal volumes of ethyl acetate R
and methanol R.
Apply separately to the plate 5 l of each solution. Develop
over a path of 15 cm using a mixture of 6 volumes of
diethylamine R, 15 volumes of cyclohexane R and
79 volumes of ethanol R. Dry the plate in a current of
warm air for 5 min. Allow to cool and spray with a freshly
prepared 5.0 g/l solution of potassium ferricyanide R in
ferric chloride solution R2. Examine in daylight. Any spot
in the chromatogram obtained with test solution (a), apart
from the principal spot, is not more intense than the spot
in the chromatogram obtained with reference solution (b)
(0.5 per cent) and at most one such spot is more intense
than the spot in the chromatogram obtained with reference
solution (c) (0.25 per cent).
Loss on drying (2.2.32). Not more than 1.0 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 0.1 per cent,
determined on 1.0 g.
ASSAY
Dissolve 0.200 g in a mixture of 20 ml of anhydrous acetic
acid R and 20 ml of acetic anhydride 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 29.68 mg of
C16H25ClN2O.

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