EUROPEAN PHARMACOPOEIA 9.

0 Nitrogen

(2.2.25) at the absorption maximum at 367 nm, using the Assay. Gas chromatography (2.2.28).
sodium acetate solution described above as compensation Gas to be examined. The substance to be examined.
liquid.
Reference gas (a). Ambient air.
Calculate the content of C8H6N4O5, taking the specific
Reference gas (b). Nitrogen R1.
absorbance to be 765.
Column :
STORAGE – material : stainless steel ;
Store protected from light, at a temperature below 25 °C. – size : l = 2 m, Ø = 2 mm ;
– stationary phase : molecular sieve for chromatography R
(0.5 nm).
01/2008:1247 Carrier gas : helium for chromatography R.
Flow rate : 40 mL/min.
Temperature :
– column : 50 °C ;
NITROGEN – detection : 130 °C.
Detection : thermal conductivity.
Nitrogenium Injection : loop injector.
Inject reference gas (a). Adjust the injected volumes and
N2 Mr 28.01 operating conditions so that the height of the peak due to
[7727-37-9] nitrogen in the chromatogram obtained with the reference gas
is at least 35 per cent of the full scale of the recorder.
DEFINITION
System suitability :
Content : minimum 99.5 per cent V/V of N2.
– the chromatograms obtained show a clear separation of
This monograph applies to nitrogen for medicinal use. oxygen and nitrogen.
CHARACTERS Calculate the content of N2 in the gas to be examined.
Appearance : colourless, odourless gas. IDENTIFICATION
Solubility : at 20 °C and at a pressure of 101 kPa, 1 volume First identification : A.
dissolves in about 62 volumes of water and about 10 volumes
Second identification : B, C.
of ethanol (96 per cent).
A. Examine the chromatograms obtained in the assay (see
PRODUCTION Production).
Carbon dioxide : maximum 300 ppm V/V, determined using Results : the principal peak in the chromatogram obtained
an infrared analyser (2.5.24). with the substance to be examined is similar in retention
Gas to be examined. The substance to be examined. It must be time to the principal peak in the chromatogram obtained
filtered to avoid stray light phenomena. with reference gas (b).
Reference gas (a). Nitrogen R1. B. In a 250 mL conical flask replace the air by the substance to
be examined. Place a burning or glowing splinter of wood
Reference gas (b). Mixture containing 300 ppm V/V of carbon in the flask. The splinter is extinguished.
dioxide R1 in nitrogen R1.
C. In a suitable test tube, place 0.1 g of magnesium R in
Calibrate the apparatus and set the sensitivity using reference turnings. Close the tube with a two-hole stopper fitted with
gases (a) and (b). Measure the content of carbon dioxide in a glass tube reaching about 1 cm above the turnings. Pass
the gas to be examined. the substance to be examined through the glass tube for
Carbon monoxide : maximum 5 ppm V/V, determined using 1 min without heating, then for 15 min while heating the
an infrared analyser (2.5.25). test tube to a red glow. After cooling, add 5 mL of dilute
Gas to be examined. The substance to be examined. It must be sodium hydroxide solution R. The evolving vapours change
filtered to avoid stray light phenomena. the colour of moistened red litmus paper R blue.
Reference gas (a). Nitrogen R1. TESTS
Reference gas (b). Mixture containing 5 ppm V/V of carbon Carbon dioxide (2.1.6) : maximum 300 ppm V/V, determined
monoxide R in nitrogen R1. using a carbon dioxide detector tube.
Calibrate the apparatus and set the sensitivity using reference Carbon monoxide (2.1.6): maximum 5 ppm V/V, determined
gases (a) and (b). Measure the content of carbon monoxide in using a carbon monoxide detector tube.
the gas to be examined.
Water vapour (2.1.6) : maximum 67 ppm V/V, determined
Oxygen : maximum 50 ppm V/V, determined using an oxygen using a water vapour detector tube.
analyser with a detector scale ranging from 0-100 ppm V/V
and equipped with an electrochemical cell. STORAGE
The gas to be examined passes through a detection cell As a compressed gas or a liquid in appropriate containers
containing an aqueous solution of an electrolyte, generally complying with the legal regulations.
potassium hydroxide. The presence of oxygen in the gas to be
examined produces variation in the electric signal recorded at IMPURITIES
the outlet of the cell that is proportional to the oxygen content. Specified impurities : A, B, C, D.
Calibrate the analyser according to the instructions of the
A. CO2 : carbon dioxide,
manufacturer. Pass the gas to be examined through the
analyser using a suitable pressure regulator and airtight metal B. CO : carbon monoxide,
tubes and operating at the prescribed flow-rates until constant
readings are obtained. C. O2 : oxygen,
Water (2.5.28) : maximum 67 ppm V/V. D. H2O : water.

General Notices (1) apply to all monographs and other texts 3165
Nitrogen, low-oxygen EUROPEAN PHARMACOPOEIA 9.0

01/2008:1685 A. Examine the chromatograms obtained in the test for

impurities (see Production).
Results : the principal peak in the chromatogram obtained
with the gas to be examined is similar in retention time
to the principal peak in the chromatogram obtained with
NITROGEN, LOW-OXYGEN reference gas (b).
B. In a 250 mL conical flask replace the air by the gas to be
Nitrogenium oxygenio depletum examined. Place a burning or glowing splinter of wood in
the flask. The splinter is extinguished.
N2 Mr 28.01 C. In a suitable test tube, place 0.1 g of magnesium R in
turnings. Close the tube with a two-hole stopper fitted with
DEFINITION
a glass tube reaching about 1 cm above the turnings. Pass
This monograph applies to nitrogen which is used for inerting the gas to be examined through the glass tube for 1 min
finished medicinal products which are particularly sensitive without heating, then for 15 min while heating the test tube
to degradation by oxygen. It does not necessarily apply to to a red glow. After cooling, add 5 mL of dilute sodium
nitrogen used in earlier production steps. hydroxide solution R. The evolving vapours turn the colour
Content : minimum 99.5 per cent V/V of N2, calculated by of moistened red litmus paper R blue.
deduction of the sum of impurities found when performing
the test for impurities. STORAGE
Where the gas has to be stored, store as a compressed gas or
CHARACTERS a liquid in appropriate containers complying with the legal
Colourless and odourless gas. regulations.
Solubility : at 20 °C and at a pressure of 101 kPa, 1 volume
IMPURITIES
dissolves in about 62 volumes of water and about 10 volumes
of alcohol. A. O2 : oxygen,
PRODUCTION B. Ar : argon.
Oxygen : maximum 5 ppm V/V, determined using an oxygen
analyser with a detector scale ranging from 0 ppm V/V to 01/2008:0416
100 ppm V/V and equipped with an electrochemical cell.
The gas to be examined passes through a detection cell
containing an aqueous solution of an electrolyte, generally
potassium hydroxide. The presence of oxygen in the gas to be
examined produces variation in the electric signal recorded at NITROUS OXIDE
the outlet of the cell that is proportional to the oxygen content.
Calibrate the analyser according to the manufacturer’s Dinitrogenii oxidum
instructions. Pass the gas to be examined through the analyser
using a suitable pressure regulator and airtight metal tubes N2O Mr 44.01
and operating at the prescribed flow rates until constant [10024-97-2]
readings are obtained.
DEFINITION
Impurities. Gas chromatography (2.2.28).
Content : minimum 98.0 per cent V/V of N2O in the gaseous
Gas to be examined. The substance to be examined. phase, when sampled at 15 °C.
Reference gas (a). Use ambient air. This monograph applies to nitrous oxide for medicinal use.
Reference gas (b). Use nitrogen R1.
Column : CHARACTERS
– material : stainless steel, Appearance : colourless gas.
– size : l = 2 m, Ø = 2 mm, Solubility : at 20 °C and at a pressure of 101 kPa, 1 volume
– stationary phase : appropriate molecular sieve for dissolves in about 1.5 volumes of water.
chromatography (0.5 nm). PRODUCTION
Carrier gas : helium for chromatography R. Nitrous oxide is produced from ammonium nitrate by thermic
Flow rate : 40 mL/min. decomposition.
Temperature : Examine the gaseous phase.
– column : 50 °C, If the test is performed on a cylinder, keep the cylinder at
– detector : 130 °C. room temperature for at least 6 h before carrying out the tests.
Detection : thermal conductivity. Keep the cylinder in the vertical position with the outlet valve
System suitability : reference gas (a) : adjust the injected uppermost.
volumes and operating conditions so that the height of the Carbon dioxide. Gas chromatography (2.2.28).
peak due to nitrogen in the chromatogram obtained is at least Gas to be examined. The substance to be examined.
35 per cent of the full scale of the recorder : Reference gas. A mixture containing 300 ppm V/V of carbon
– the chromatogram obtained shows a clear separation of dioxide R1 in nitrous oxide R.
oxygen and nitrogen. Column :
Limit : – material : stainless steel ;
– total : not more than 0.5 per cent of the sum of the areas of – size : l = 3.5 m, Ø = 2 mm ;
all the peaks (0.5 per cent V/V).
– stationary phase : ethylvinylbenzene-divinylbenzene
IDENTIFICATION copolymer R.
First identification : A. Carrier gas : helium for chromatography R.
Second identification : B, C. Flow rate : 15 mL/min.

3166 See the information section on general monographs (cover pages)