Svensk läkemedelsstandard

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1 Svensk läkemedelsstandard Nitrous oxide Postadress/Postal address: P.O. Box 26, SE Uppsala, SWEDEN Besöksadress/Visiting address: Dag Hammarskjölds väg 42, Uppsala Telefon/Phone: +46 (0) Fax: +46 (0) Internet:

2 Ansvarig utgivare: Svenska farmakopékommittén Läkemedelsverket Box 26 S Uppsala, Sweden Tel. 018/ (6)

3 NITROUS OXIDE 1 Dinitrogenii oxidum N 2 O M r [ ] DEFINITION Content: minimum 98.0 per cent V/V of N 2 O in the gaseous phase, 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 volume dissolves in about 1.5 volumes of water. PRODUCTION Nitrous oxide is produced from ammonium nitrate by thermic decomposition. 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). Gas to be examined. The substance to be examined. Reference gas. A mixture containing 300 ppm V/V of carbon dioxide R1 in nitrous oxide R. Column: - material: stainless steel; - size: l = 3.5 m, Ø = 2 mm; - stationary phase: ethylvinylbenzene-divinylbenzene copolymer R. Carrier gas: helium for chromatography R. Flow rate: 15 ml/min. Temperature: - column: 40 C; 1 Kapitlet är hämtat från Ph Eur 9th Ed för information. I händelse av tvist gäller alltid det vid tillfället giltiga kapitlet i Ph Eur. 3(6)

4 - detector: 90 C. Detection: thermal conductivity. Injection: loop injector. Adjust the injected volumes and operating conditions so that the height of the peak due to carbon dioxide in the chromatogram obtained with the reference gas is at least 35 per cent of the full scale of the recorder. The test is not valid unless the chromatograms obtained show a clear separation of carbon dioxide from nitrous oxide. Limit: - carbon dioxide: not more than the area of the corresponding peak in the chromatogram obtained with the reference gas (300 ppm V/V). Carbon monoxide. Gas chromatography (2.2.28). When the test is carried out on a cylinder, use the first portion of gas to be withdrawn. Gas to be examined. The substance to be examined. Reference gas. A mixture containing 5 ppm V/V of carbon monoxide R in nitrous oxide R. Column: - material: stainless steel; - size: l = 2 m, Ø = 4 mm; - stationary phase: suitable molecular sieve for chromatography (0.5 nm). Carrier gas: helium for chromatography R. Flow rate: 60 ml/min. Temperature: - column: 50 C; - injection port and detector: 130 C. Detection: flame ionisation with methaniser. Injection: loop injector. Adjust the injected volumes and the operating conditions so that the height of the peak due to carbon monoxide in the chromatogram obtained with the reference gas is at least 35 per cent of the full scale of the recorder. Limit: - carbon monoxide: not more than the area of the corresponding peak in the chromatogram obtained with the reference gas (5 ppm V/V). 4(6)

5 Nitrogen monoxide and nitrogen dioxide: maximum 2 ppm V/V in total in the gaseous and liquid phases, determined using a chemiluminescence analyser (2.5.26). Gas to be examined. The substance to be examined. Reference gas (a). Nitrous oxide R. Reference gas (b). A mixture containing 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, separately examining the samples collected from the gaseous phase and the liquid phase of the gas to be examined. Multiply the result obtained by the quenching correction factor in order to correct the quenching effect on the analyser response caused by the nitrous oxide matrix effect. The quenching correction factor is determined by applying a known reference mixture of nitrogen monoxide in nitrous oxide and comparing the actual content with the content indicated by the analyser which has been calibrated with an NO/N 2 reference mixture. Quenching correction factor = actual nitrogen monooxide content indicated nitrogen monooxide content Water: maximum 67 ppm V/V, determined using an electrolytic hygrometer (2.5.28). Assay. Infrared analyser (2.5.35). Gas to be examined. The substance to be examined. It must be filtered to avoid stray light phenomena. Reference gas (a). Nitrous oxide R. Reference gas (b). A mixture containing 5.0 per cent V/V of nitrogen R1 and 95.0 per cent V/V of nitrous oxide R. Calibrate the apparatus and set the sensitivity using reference gases (a) and (b). Measure the content of nitrous oxide in the gas to be examined. IDENTIFICATION First identification: A. Second identification: B, C. A. It complies with the limits of the assay. B. Place a glowing splinter of wood in the substance to be examined. The splinter bursts into flame. C. Introduce the substance to be examined into alkaline pyrogallol solution R. A brown colour does not develop. 5(6)

6 TESTS Examine the gaseous phase. If the test is performed on a cylinder, keep the cylinder of the substance to be examined 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: maximum 300 ppm V/V, determined using a carbon dioxide detector tube (2.1.6). Carbon monoxide: maximum 5 ppm V/V, determined using a carbon monoxide detector tube (2.1.6). When the test is carried out on a cylinder, use the first portion of the gas to be withdrawn. Nitrogen monoxide and nitrogen dioxide: maximum 2 ppm V/V, determined using a nitrogen monoxide and nitrogen dioxide detector tube (2.1.6). Water vapour: maximum 67 ppm V/V, determined using a water vapour detector tube (2.1.6). STORAGE Store liquefied under pressure in suitable containers complying with the legal regulations. The taps and valves are not greased or oiled. IMPURITIES Specified impurities: A, B, C, D, E. A. carbon dioxide, B. carbon monoxide, C. nitrogen monoxide, D. nitrogen dioxide, E. water 6(6)