Air, medicinal

EUROPEAN PHARMACOPOEIA 7.0

Reference solution (b). Dissolve 1.5 mg of noradrenaline

tartrate CRS (impurity B) and 1.5 mg of adrenalone
hydrochloride R (impurity C) in solvent mixture B, add
1.0 mL of the test solution and dilute to 100.0 mL with solvent
mixture B.
Reference solution (c). Dissolve the contents of a vial of
adrenaline impurity mixture CRS (impurities D and E) in
0.1 mL of 0.1 M hydrochloric acid and 0.9 mL of solvent
mixture B.
Reference solution (d). Dissolve 7.5 mg of adrenaline tartrate
with impurity A CRS in 0.5 mL of 0.1 M hydrochloric acid and
dilute to 5.0 mL with solvent mixture B.
Blank solution : 0.1 M hydrochloric acid, solvent mixture B
(1:9 V/V).
Column :
size : l = 0.10 m, = 4.6 mm ;
stationary phase : end-capped octadecylsilyl silica gel for
chromatography R (3 m) ;
temperature : 50 C.
Mobile phase :
mobile phase A : acetonitrile R1, solvent mixture A
(5:95 V/V) ;
mobile phase B : acetonitrile R1, solvent mixture A
(45:55 V/V) ;
Time
(min)
0 - 15

Mobile phase A
(per cent V/V)
92 50

Mobile phase B
(per cent V/V)
8 50

15 - 20

50 92

50 8

20 - 25

92

Flow rate: 2.0 mL/min.

Detection : spectrophotometer at 210 nm.
Injection : 20 L.
Identification of impurities : use the chromatogram supplied
with adrenaline impurity mixture CRS and the chromatogram
obtained with reference solution (c) to identify the peaks due
to impurities D and E ; use the chromatogram supplied with
adrenaline tartrate with impurity A CRS and the chromatogram
obtained with reference solution (d) to identify the peak due
to impurity A.
Relative retention with reference to adrenaline
(retention time = about 4 min) : impurity B = about 0.8 ;
impurity C = about 1.3 ; impurity A = about 3.2 ;
impurity D = about 3.3 ; impurity E = about 3.7.
System suitability : reference solution (b) :
resolution : minimum 3.0 between the peaks due to
impurity B and adrenaline.
Limits :
correction factors : for the calculation of content, multiply the
peak areas of the following impurities by the corresponding
correction factor : impurity D = 0.7 ; impurity E = 0.6 ;
impurity A : not more than 3 times the area of the principal
peak in the chromatogram obtained with reference
solution (a) (0.3 per cent) ;
impurities B, C : for each impurity, not more than twice the
area of the principal peak in the chromatogram obtained
with reference solution (a) (0.2 per cent) ;
impurities D, E : for each impurity, not more than the area
of the principal peak in the chromatogram obtained with
reference solution (a) (0.1 per cent) ;
unspecified impurities : for each impurity, not more than the
area of the principal peak in the chromatogram obtained
with reference solution (a) (0.10 per cent) ;
total : not more than 6 times the area of the principal peak
in the chromatogram obtained with reference solution (a)
(0.6 per cent) ;
General Notices (1) apply to all monographs and other texts

disregard limit : 0.5 times the area of the principal peak

in the chromatogram obtained with reference solution (a)
(0.05 per cent).
Loss on drying (2.2.32) : maximum 0.5 per cent, determined on
1.000 g by drying in vacuo for 18 h.
Sulfated ash (2.4.14): maximum 0.1 per cent, determined on
1.0 g.
ASSAY
Dissolve 0.300 g in 50 mL of anhydrous acetic acid R, heating
gently if necessary. Titrate with 0.1 M perchloric acid until a
bluish-green colour is obtained, using 0.1 mL of crystal violet
solution R as indicator.
1 mL of 0.1 M perchloric acid is equivalent to 33.33 mg
of C13H19NO9.
STORAGE
In an airtight container, or preferably in a sealed tube under
vacuum or under an inert gas, protected from light.
IMPURITIES
Specified impurities : A, B, C, D, E.
A. unknown structure,

B. (1R)-2-amino-1-(3,4-dihydroxyphenyl)ethanol (noradrenaline),

C. 1-(3,4-dihydroxyphenyl)-2-(methylamino)ethanone
(adrenalone),

D. 4-[(1R)-2-(benzylmethylamino)-1-hydroxyethyl]benzene-1,2diol,

E. 2-(benzylmethylamino)-1-(3,4-dihydroxyphenyl)ethanone.
01/2009:1238

AIR, MEDICINAL
Aer medicinalis
DEFINITION
Compressed ambient air.
Content : 20.4 per cent V/V to 21.4 per cent V/V of oxygen (O2).
CHARACTERS
Appearance: colourless gas.
Solubility : at 20 C at a pressure of 101 kPa, 1 volume dissolves
in about 50 volumes of water.
1331

Air, medicinal

EUROPEAN PHARMACOPOEIA 7.0

PRODUCTION
Carbon dioxide : maximum 500 ppm V/V, determined using
an infrared analyser (2.5.24).
Gas to be examined. Filter the substance to be examined to
avoid stray light phenomena.
Reference gas (a). Use a mixture of 21 per cent V/V of oxygen R
and 79 per cent V/V of nitrogen R1, containing less than
1 ppm V/V of carbon dioxide R1.
Reference gas (b). Use a mixture of 21 per cent V/V of oxygen R
and 79 per cent V/V of nitrogen R1, containing 500 ppm V/V
of carbon dioxide 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 : maximum 5 ppm V/V, determined using
an infrared analyser (2.5.25).
Gas to be examined. Filter the substance to be examined to
avoid stray light phenomena.
Reference gas (a). Use a mixture of 21 per cent V/V of oxygen R
and 79 per cent V/V of nitrogen R1, containing less than
1 ppm V/V of carbon monoxide R.
Reference gas (b). Use a mixture of 21 per cent V/V of oxygen R
and 79 per cent V/V of nitrogen R1, containing 5 ppm V/V of
carbon monoxide R.
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.
Sulfur dioxide : maximum 1 ppm V/V, determined using an
ultraviolet fluorescence analyser (Figure 1238.-1).
The apparatus consists of the following :
a system generating ultraviolet radiation with a wavelength
of 210 nm, made up of an ultraviolet lamp, a collimator, and a
selective filter; the beam is blocked periodically by a chopper
rotating at high speeds ;
a reaction chamber, through which flows the gas to be
examined ;
a system that detects radiation emitted at a wavelength of
350 nm, made up of a selective filter, a photomultiplier tube
and an amplifier.
Gas to be examined. Filter the substance to be examined.
Reference gas (a). Use a mixture of 21 per cent V/V of oxygen R
and 79 per cent V/V of nitrogen R1.

Reference gas (b). Use a mixture of 21 per cent V/V of oxygen R

and 79 per cent V/V of nitrogen R1, containing 0.5 ppm V/V to
2 ppm V/V of sulfur dioxide R1.
Calibrate the apparatus and set the sensitivity using reference
gases (a) and (b). Measure the content of sulfur dioxide in the
gas to be examined.
Oil : maximum 0.1 mg/m3, determined using an oil detector
tube (2.1.6), when an oil-lubricated compressor is used for the
production.
Nitrogen monoxide and nitrogen dioxide : maximum 2 ppm V/V
in total, determined using a chemiluminescence analyser
(2.5.26).
Gas to be examined. The substance to be examined.
Reference gas (a). Use a mixture of 21 per cent V/V of oxygen R
and 79 per cent V/V of nitrogen R1, containing less than
0.05 ppm V/V of nitrogen monoxide and nitrogen dioxide.
Reference gas (b). Use a mixture of 2 ppm V/V of nitrogen
monoxide R in nitrogen R1.
Calibrate the apparatus and set the sensitivity using reference
gases (a) and (b). Measure the content of nitrogen monoxide
and nitrogen dioxide in the gas to be examined.
Water : maximum 67 ppm V/V, determined using an electrolytic
hygrometer (2.5.28), except where the competent authority
decides that the following limit applies to medicinal air
generated on-site and distributed in pipe-line systems operating
at a pressure not greater than 10 bars and a temperature not
less than 5 C : maximum 870 ppm V/V, determined using an
electrolytic hygrometer (2.5.28).
Assay. Determine the concentration of oxygen in air using a
paramagnetic analyser (2.5.27).
IDENTIFICATION
First identification : C.
Second identification : A, B.
A. In a conical flask containing the substance to be examined,
place a glowing wood splinter. The splinter remains glowing.
B. Use a gas burette (Figure 1238.-2) of 25 mL capacity in the
form of a chamber in the middle of which is a tube graduated
in 0.2 per cent between 19.0 per cent and 23.0 per cent,
and isolated at each end by a tap with a conical barrel. The
lower tap is joined to a tube with an olive-shaped nozzle
and is used to introduce the gas into the apparatus. A
cylindrical funnel above the upper tap is used to introduce
the absorbent solution. Wash the burette with water R and

Figure 1238.-1. UV fluorescence analyser

1332

See the information section on general monographs (cover pages)

Air, synthetic medicinal

EUROPEAN PHARMACOPOEIA 7.0

dry. Open the 2 taps. Connect the nozzle to the source of the
gas to be examined and set the flow rate to 1 L/min. Flush
the burette by passing the gas to be examined through it for
1 min. Close the lower tap of the burette and immediately
afterwards the upper tap. Rapidly disconnect the burette
from the source of the gas to be examined. Rapidly give a
half turn to the upper tap to eliminate any excess pressure in
the burette. Keeping the burette vertical, fill the funnel with
a freshly prepared mixture of 21 mL of a 560 g/L solution of
potassium hydroxide R and 130 mL of a 200 g/L solution
of sodium dithionite R. Open the upper tap slowly. The
solution absorbs the oxygen and enters the burette. Allow
to stand for 10 min without shaking. Read the level of the
liquid meniscus on the graduated part of the burette. This
figure represents the percentage V/V of oxygen. The value
read is 20.4 to 21.4.

Oil : maximum 0.1 mg/m3, determined using an oil detector

tube (2.1.6), when an oil-lubricated compressor is used for the
production.
Nitrogen monoxide and nitrogen dioxide : maximum 2 ppm V/V,
determined using a nitrogen monoxide and nitrogen dioxide
detector tube (2.1.6).
Carbon monoxide : maximum 5 ppm V/V, determined using a
carbon monoxide detector tube (2.1.6).
Water vapour : maximum 67 ppm V/V, determined using a
water vapour detector tube (2.1.6), except where the competent
authority decides that the following limit applies to medicinal air
generated on-site and distributed in pipe-line systems operating
at a pressure not greater than 10 bars and a temperature not
less than 5 C : maximum 870 ppm V/V, determined using a
water vapour detector tube (2.1.6).
STORAGE
As a gas, in suitable containers complying with the legal
regulations or as a gas supplied by a pipe network.
LABELLING
Where applicable, the label states the production method, as
regards to the use of an oil - lubricated compression.
IMPURITIES
A. CO2 : carbon dioxide,
B. SO2 : sulfur dioxide,
C. NO : nitrogen monoxide,
D. NO2 : nitrogen dioxide,
E. oil,
F. CO : carbon monoxide,
G. H2O : water.
01/2008:1684

AIR, SYNTHETIC MEDICINAL

Aer medicinalis artificiosus
DEFINITION
Mixture of Nitrogen (1247) and Oxygen (0417).
Content : 95.0 per cent to 105.0 per cent of the nominal value
which is between 21.0 per cent V/V to 22.5 per cent V/V of
oxygen (O2).
CHARACTERS
Colourless and odourless gas.
Solubility : at a temperature of 20 C and a pressure of 101 kPa,
1 volume dissolves in about 50 volumes of water.
PRODUCTION
Water (2.5.28) : maximum 67 ppm V/V.
Assay (2.5.27). Carry out the determination of oxygen in gases.
IDENTIFICATION
First identification : C.
Second identification : A, B.
A. In a conical flask containing the substance to be examined,
place a glowing splinter of wood. The splinter remains
Figure 1238.-2. Gas burette
glowing.
C. It complies with the limits of the assay.
B. Use a gas burette (Figure 1684.-1) of 25 mL capacity in
the form of a chamber, in the middle of which is a tube
graduated in 0.2 per cent between 19.0 per cent and 23.0 per
TESTS
cent, and isolated at each end by a tap with a conical barrel.
Carbon dioxide : maximum 500 ppm V/V, determined using a
The lower tap is joined to a tube with an olive-shaped nozzle
carbon dioxide detector tube (2.1.6).
and is used to introduce the gas into the apparatus. A
Sulfur dioxide : maximum 1 ppm V/V, determined using a sulfur
cylindrical funnel above the upper tap is used to introduce
dioxide detector tube (2.1.6).
the absorbent solution. Wash the burette with water R and
General Notices (1) apply to all monographs and other texts

1333