EUROPEAN PHARMACOPOEIA 6.

0 Nitrogen

100.0 ml with water R. Prepare a reference solution in the TESTS

same manner using 60.0 mg of nitrofural CRS. Measure the Related substances. Examine by thin-layer chromatography
absorbances (2.2.25) of the 2 solutions at the absorption (2.2.27), using silica gel HF254 R as the coating substance.
maximum at 375 nm.
Test solution. Dissolve 0.25 g of the substance to be
Calculate the content of C6H6N4O4 from the absorbances examined in a minimum of dimethylformamide R and dilute
measured and the concentrations of the solutions. to 10 ml with acetone R.
STORAGE Reference solution. Dilute 1 ml of the test solution to 100 ml
with acetone R.
Protected from light.
Apply separately to the plate 10 µl of each solution. Develop
IMPURITIES over a path of 15 cm using a mixture of 10 volumes of
Specified impurities : A, B. methanol R and 90 volumes of nitromethane R. Allow
the plate to dry in air and heat at 100 °C to 105 °C for
5 min. Examine in ultraviolet light at 254 nm. Spray with
phenylhydrazine hydrochloride solution R. Heat the plate
at 100 °C to 105 °C for a further 10 min. When examined
in ultraviolet light and after spraying, any spot in the
A. bis[(5-nitrofuran-2-yl)methylene]diazane, 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 (1.0 per
cent).
Loss on drying (2.2.32). Not more than 1.0 per cent,
determined on 1.00 g by drying in an oven at 105 °C.
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on 1.0 g.
ASSAY
B. (5-nitrofuran-2-yl)methylene diacetate.
Carry out the assay protected from bright light. Dissolve
0.120 g in 50 ml of dimethylformamide R and dilute to
1000.0 ml with water R. Dilute 5.0 ml of the solution to
01/2008:0101 100.0 ml with a solution containing 18 g/l of sodium
corrected 6.0 acetate R and 0.14 per cent V/V of glacial acetic acid R.
Measure the absorbance (2.2.25) at the absorption maximum
at 367 nm, using the sodium acetate solution described
NITROFURANTOIN above as compensation liquid.
Calculate the content of C8H6N4O5, taking the specific
Nitrofurantoinum absorbance to be 765.
STORAGE
Store protected from light, at a temperature below 25 °C.

01/2008:1247
C 8H 6N4O 5 Mr 238.2
[67-20-9] NITROGEN
DEFINITION
Nitrogenium
Nitrofurantoin contains not less than 98.0 per cent and
not more than the equivalent of 102.0 per cent of 1-[[(5-
nitrofuran-2-yl)methylene]amino]imidazolidine-2,4-dione, N2 Mr 28.01
calculated with reference to the dried substance. [7727-37-9]

CHARACTERS DEFINITION
Nitrogen contains not less than 99.5 per cent V/V of N2.
A yellow, crystalline powder or yellow crystals, odourless
or almost odourless, very slightly soluble in water and in This monograph applies to nitrogen for medicinal use.
alcohol, soluble in dimethylformamide.
CHARACTERS
IDENTIFICATION A colourless, odourless gas. At 20 °C and at a pressure of
A. Carry out the test protected from bright light. Use the 101 kPa, 1 volume dissolves in about 62 volumes of water
solution prepared for the assay. Examined between and about 10 volumes of alcohol.
220 nm and 400 nm (2.2.25), the solution shows two PRODUCTION
absorption maxima, at 266 nm and 367 nm. The ratio of
the absorbance at the maximum at 367 nm to that at the Carbon dioxide. Not more than 300 ppm V/V, determined
maximum at 266 nm is 1.36 to 1.42. using an infrared analyser (2.5.24).
B. Dissolve about 10 mg in 10 ml of dimethylformamide R. Gas to be examined. The substance to be examined. It must
To 1 ml of the solution add 0.1 ml of 0.5 M alcoholic be filtered to avoid stray light phenomena.
potassium hydroxide. A brown colour develops. Reference gas (a). Use nitrogen R1.

General Notices (1) apply to all monographs and other texts 2513
Nitrogen, low-oxygen EUROPEAN PHARMACOPOEIA 6.0

Reference gas (b). Use a mixture containing 300 ppm V/V B. In a 250 ml conical flask replace the air by the substance
of carbon dioxide R1 in nitrogen R1. to be examined. Place a burning or glowing splinter of
Calibrate the apparatus and set the sensitivity using wood in the flask. The splinter is extinguished.
reference gases (a) and (b). Measure the content of carbon C. In a suitable test tube, place 0.1 g of magnesium R in
dioxide in the gas to be examined. turnings. Close the tube with a two-hole stopper fitted
Carbon monoxide. Not more than 5 ppm V/V, determined with a glass tube reaching about 1 cm above the turnings.
using an infrared analyser (2.5.25). Pass the substance to be examined through the glass
tube for 1 min without heating, then for 15 min while
Gas to be examined. The substance to be examined. It must heating the test tube to a red glow. After cooling, add
be filtered to avoid stray light phenomena. 5 ml of dilute sodium hydroxide solution R. The evolving
Reference gas (a). Use nitrogen R1. vapours change the colour of moistened red litmus
Reference gas (b). Use a mixture containing 5 ppm V/V of paper R blue.
carbon monoxide R in nitrogen R1.
TESTS
Calibrate the apparatus and set the sensitivity using
reference gases (a) and (b). Measure the content of carbon Carbon dioxide. Not more than 300 ppm V/V, determined
monoxide in the gas to be examined. using a carbon dioxide detector tube (2.1.6).
Oxygen. Not more than 50 ppm V/V, determined using Carbon monoxide. Not more than 5 ppm V/V, determined
an oxygen analyser with a detector scale ranging from using a carbon monoxide detector tube (2.1.6).
0 ppm V/V to 100 ppm V/V and equipped with an Water vapour. Not more than 67 ppm V/V, determined
electrochemical cell. using a water vapour detector tube (2.1.6).
The gas to be examined passes through a detection cell
STORAGE
containing an aqueous solution of an electrolyte, generally
potassium hydroxide. The presence of oxygen in the gas Store as a compressed gas or a liquid in appropriate
to be examined produces variation in the electric signal containers complying with the legal regulations.
recorded at the outlet of the cell that is proportional to the IMPURITIES
oxygen content.
Calibrate the analyser according to the instructions of the A. carbon dioxide,
manufacturer. Pass the gas to be examined through the B. carbon monoxide,
analyser using a suitable pressure regulator and airtight
metal tubes and operating at the prescribed flow-rates until C. oxygen,
constant readings are obtained. D. water.
Water. Not more than 67 ppm V/V, determined using an
electrolytic hygrometer (2.5.28).
Assay. Examine by gas chromatography (2.2.28). 01/2008:1685
Gas to be examined. The substance to be examined.
Reference gas (a). Use ambient air.
NITROGEN, LOW-OXYGEN
Reference gas (b). Use nitrogen R1. Nitrogenium oxygenio depletum
The chromatographic procedure may be carried out using :
— a stainless steel column 2 m long and 2 mm in internal N2 Mr 28.01
diameter packed with an appropriate molecular sieve for
chromatography (0.5 nm), DEFINITION
— helium for chromatography R as the carrier gas at a flow This monograph applies to nitrogen which is used for
rate of 40 ml/min, inerting finished medicinal products which are particularly
— a thermal conductivity detector, sensitive to degradation by oxygen. It does not necessarily
apply to nitrogen used in earlier production steps.
— a loop injector,
Content : minimum 99.5 per cent V/V of N2, calculated by
maintaining the temperature of the column at 50 °C and deduction of the sum of impurities found when performing
that of the detector at 130 °C. the test for impurities.
Inject reference gas (a). Adjust the injected volumes and
operating conditions so that the height of the peak due to CHARACTERS
nitrogen in the chromatogram obtained with the reference Colourless and odourless gas.
gas is at least 35 per cent of the full scale of the recorder. Solubility : at 20 °C and at a pressure of 101 kPa, 1 volume
The assay is not valid unless the chromatograms obtained dissolves in about 62 volumes of water and about 10 volumes
show a clear separation of oxygen and nitrogen. of alcohol.
Inject the gas to be examined and reference gas (b). Calculate
the content of N2 in the gas to be examined. PRODUCTION
Oxygen : maximum 5 ppm V/V, determined using an oxygen
IDENTIFICATION
analyser with a detector scale ranging from 0 ppm V/V to
First identification : A. 100 ppm V/V and equipped with an electrochemical cell.
Second identification : B, C. The gas to be examined passes through a detection cell
A. Examine the chromatograms obtained in the Assay. The containing an aqueous solution of an electrolyte, generally
retention time of the principal peak in the chromatogram potassium hydroxide. The presence of oxygen in the gas
obtained with the substance to be examined is to be examined produces variation in the electric signal
approximately the same as that of the principal peak in recorded at the outlet of the cell that is proportional to the
the chromatogram obtained with reference gas (b). oxygen content.

2514 See the information section on general monographs (cover pages)