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Nitrogen EUROPEAN PHARMACOPOEIA 7.0

ASSAY

Carry out the assay protected from bright light . Dissolve0.120 g in 50 mL of dimethylformamide R and dilute to1000.0 mL with water R. Dilute 5.0 mL of the solution to100.0 mL with a solution containing 18 g/L of sodiumacetate R and 0.14 per cent V/V of glacial acetic acid R.Measure the absorbance ( 2.2.25 ) at the absorption maximumat 367 nm, using the sodium acetate solution described above

as compensation liquid.Calculate the content of C8H6N4O5, taking the specificabsorbance to be 765.

STORAGE

Store protected from light, at a temperature below 25 °C.

01/2008:1247

NITROGEN

Nitrogenium

N2 M r 28.01[7727-37-9]

DEFINITION

Content : minimum 99.5 per cent V/V of N2.

This monograph applies to nitrogen for medicinal use.

CHARACTERS

Appearance : colourless, odourless gas.

Solubility : at 20 °C and at a pressure of 101 kPa, 1 volumedissolves in about 62 volumes of water and about 10 volumesof ethanol (96 per cent).

PRODUCTION

Carbon dioxide : maximum 300 ppm V/V , determined using

an infrared analyser ( 2.5.24).Gas to be examined . The substance to be examined. It must befiltered to avoid stray light phenomena.

Reference gas (a). Nitrogen R1.

Reference gas (b). Mixture containing 300 ppm V/V of carbondioxide R1 in nitrogen R1.

Calibrate the apparatus and set the sensitivity using referencegases (a) and (b). Measure the content of carbon dioxide in thegas to be examined.

Carbon monoxide : maximum 5 ppm V/V , determined usingan infrared analyser ( 2.5.25 ).

Gas to be examined . The substance to be examined. It must befiltered to avoid stray light phenomena.

Reference gas (a). Nitrogen R1. Reference gas (b). Mixture containing 5 ppm V/V of carbonmonoxide R in nitrogen R1.

Calibrate the apparatus and set the sensitivity using referencegases (a) and (b). Measure the content of carbon monoxide inthe gas to be examined.

Oxygen : maximum 50 ppm V/V , determined using an oxygenanalyser with a detector scale ranging from 0-100 ppm V/V andequipped with an electrochemical cell.

The gas to be examined passes through a detection cellcontaining an aqueous solution of an electrolyte, generallypotassium hydroxide. The presence of oxygen in the gas to beexamined produces variation in the electric signal recorded at the outlet of the cell that is proportional to the oxygen content.

Calibrate the analyser according to the instructions of themanufacturer. Pass the gas to be examined through theanalyser using a suitable pressure regulator and airtight metaltubes and operating at the prescribed flow-rates until constant readings are obtained.

Water ( 2.5.28 ): maximum 67 ppm V/V .

Assay. Gas chromatography ( 2.2.28 ).

Gas to be examined . The substance to be examined.

Reference gas (a). Ambient air.

Reference gas (b). Nitrogen R1.

Column :

— material : stainless steel;

— size : l = 2 m, Ø = 2 mm ;

— stationary phase : molecular sieve for chromatography R(0.5 nm).

Carrier gas : helium for chromatography R.

Flow rate : 40 mL/min.

Temperature :

— column : 50 °C;

— detection : 130 °C.

Detection : thermal conductivity.

Injection : loop injector.

Inject reference gas (a). Adjust the injected volumes andoperating conditions so that the height of the peak due tonitrogen in the chromatogram obtained with the reference gasis at least 35 per cent of the full scale of the recorder.

System suitability :

— the chromatograms obtained show a clear separation of oxygen and nitrogen.

Calculate the content of N2 in the gas to be examined.

IDENTIFICATION

First identification : A.

Second identification : B, C.

A. Examine the chromatograms obtained in the assay (seeProduction).

Results: the principal peak in the chromatogram obtainedwith the substance to be examined is similar in retention

time to the principal peak in the chromatogram obtainedwith reference gas (b).

B. In a 250 mL conical flask replace the air by the substance tobe examined. Place a burning or glowing splinter of wood inthe flask. The splinter is extinguished.

C. In a suitable test tube, place 0.1 g of magnesium R inturnings. Close the tube with a two-hole stopper fitted witha glass tube reaching about 1 cm above the turnings. Passthe substance to be examined through the glass tube for1 min without heating, then for 15 min while heating thetest tube to a red glow. After cooling, add 5 mL of dilute sodium hydroxide solution R. The evolving vapours changethe colour of moistened red litmus paper R blue.

TESTS

Carbon dioxide ( 2.1.6 ): maximum 300 ppm V/V , determinedusing a carbon dioxide detector tube.

Carbon monoxide ( 2.1.6 ): maximum 5 ppm V/V , determinedusing a carbon monoxide detector tube.

Water vapour ( 2.1.6 ): maximum 67 ppm V/V , determined usinga water vapour detector tube.

STORAGE

As a compressed gas or a liquid in appropriate containerscomplying with the legal regulations.

IMPURITIES

Specified impurities: A, B, C, D.

A. CO2 : carbon dioxide,B. CO: carbon monoxide,

C. O2 : oxygen,

D. H2O: water.

2584 See the information section on general monographs (cover pages)

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EUROPEAN PHARMACOPOEIA 7.0 Nitrous oxide

01/2008:1685

NITROGEN, LOW-OXYGEN

Nitrogenium oxygenio depletum

N2 M r 28.01

DEFINITIONThis monograph applies to nitrogen which is used for inertingfinished medicinal products which are particularly sensitive todegradation by oxygen. It does not necessarily apply to nitrogenused in earlier production steps.

Content : minimum 99.5 per cent V/V of N2, calculated bydeduction of the sum of impurities found when performing thetest for impurities.

CHARACTERS

Colourless and odourless gas.

Solubility : at 20 °C and at a pressure of 101 kPa, 1 volumedissolves in about 62 volumes of water and about 10 volumesof alcohol.

PRODUCTION

Oxygen : maximum 5 ppm V/V , determined using an oxygenanalyser with a detector scale ranging from 0 ppm V/V to100 ppm V/V and equipped with an electrochemical cell.

The gas to be examined passes through a detection cellcontaining an aqueous solution of an electrolyte, generallypotassium hydroxide. The presence of oxygen in the gas to beexamined produces variation in the electric signal recorded at the outlet of the cell that is proportional to the oxygen content.

Calibrate the analyser according to the manufacturer’sinstructions. Pass the gas to be examined through the analyserusing a suitable pressure regulator and airtight metal tubes andoperating at the prescribed flow rates until constant readings

are obtained.Impurities. Gas chromatography ( 2.2.28 ).


Reference gas (a). Use ambient air.

Reference gas (b). Use nitrogen R1.

Column :

— material : stainless steel,

— size : l = 2 m, Ø = 2 mm,

— stationary phase : appropriate molecular sieve forchromatography (0.5 nm).



Temperature :

— column : 50 °C,

— detector : 130 °C.


System suitability : reference gas (a): adjust the injectedvolumes and operating conditions so that the height of the peakdue to nitrogen in the chromatogram obtained is at least 35 percent of the full scale of the recorder:

— the chromatogram obtained shows a clear separation of oxygen and nitrogen.

Limit :

— total : not more than 0.5 per cent of the sum of the areas of all the peaks (0.5 per cent V/V ).

IDENTIFICATION First identification: A.

Second identification: B, C.

A. Examine the chromatograms obtained in the test forimpurities (see Production).

Results: the principal peak in the chromatogram obtainedwith the gas to be examined is similar in retention timeto the principal peak in the chromatogram obtained withreference gas (b).

B. In a 250 mL conical flask replace the air by the gas to beexamined. Place a burning or glowing splinter of wood inthe flask. The splinter is extinguished.

C. In a suitable test tube, place 0.1 g of magnesium R in

turnings. Close the tube with a two-hole stopper fitted witha glass tube reaching about 1 cm above the turnings. Passthe gas to be examined through the glass tube for 1 minwithout heating, then for 15 min while heating the test tubeto a red glow. After cooling, add 5 mL of dilute sodiumhydroxide solution R. The evolving vapours turn the colourof moistened red litmus paper R blue.

STORAGE

Where the gas has to be stored, store as a compressed gas ora liquid in appropriate containers complying with the legalregulations.

IMPURITIES

A. O2 : oxygen,

B. Ar: argon.

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NITROUS OXIDE

Dinitrogenii oxidum

N2O M r 44.01[10024-97-2]

DEFINITION

Content : minimum 98.0 per cent V/V of N2O in the gaseousphase, when sampled at 15 °C.

This monograph applies to nitrous oxide for medicinal use.

CHARACTERS

Appearance : colourless gas.

Solubility : at 20 °C and at a pressure of 101 kPa, 1 volumedissolves in about 1.5 volumes of water.

PRODUCTION

Nitrous oxide is produced from ammonium nitrate by thermicdecomposition.

Examine the gaseous phase.

If the test is performed on a cylinder, keep the cylinder at room temperature for at least 6 h before carrying out the tests. Keep the cylinder in the vertical position with the outlet valve

uppermost.

Carbon dioxide. Gas chromatography ( 2.2.28 ).


Reference gas. A mixture containing 300 ppm V/V of carbondioxide R1 in nitrous oxide R.

Column :

— material : stainless steel;

— size : l = 3.5 m, Ø = 2 mm;

— stationary phase : ethylvinylbenzene-divinylbenzenecopolymer R.



Temperature :

— column : 40 °C;

— detector : 90 °C.


Injection : loop injector.

General Notices (1) apply to all monographs and other texts 2585

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