EUROPEAN PHARMACOPOEIA 5.

Xenon (133Xe) injection

Bacterial endotoxins (2.6.14) : less than 175/V IU/ml, V being the maximum administered volume in millilitres. The injection may be released for use before completion of the test. CHEMICAL PURITY (a) Ammonium (2.4.1). 1 ml complies with the limit test for ammonium (10 ppm). (b) Nitrates. To 1 ml add 49 ml of nitrate-free water R. Place 5 ml of this solution in a test-tube immersed in iced water, add 0.4 ml of a 100 g/l solution of potassium chloride R, 0.1 ml of diphenylamine solution R and, dropwise with shaking, 5 ml of sulphuric acid R. Transfer the tube to a water-bath at 50 C. After 15 min, any blue colour in the solution is not more intense than that in a standard prepared at the same time in the same manner using a mixture of 4.5 ml of nitrate-free water R and 0.5 ml of nitrate standard solution (2 ppm NO3) R (10 ppm). The injection may be released for use before completion of tests (a) and (b). RADIONUCLIDIC PURITY Record the gamma-ray spectrum using a suitable instrument. The spectrum does not differ significantly from that of a standardised fluorine-18 solution. Standardised fluorine-18 solutions are available from the laboratories recognised by the competent authority. The half-life is between 1.9 min and 2.2 min. Not less than 99 per cent of total radioactivity corresponds to oxygen-15. The injection may be released for use before completion of the test. RADIOCHEMICAL PURITY Examine by liquid chromatography (2.2.29). Test solution. The preparation to be examined. The chromatographic procedure may be carried out using : a column 0.25 m long and 4.0 mm in internal diameter packed with aminopropylsilyl silica gel for chromatography R (10 m), as mobile phase at a flow rate of 1 ml/min a 10 g/l solution of potassium dihydrogen phosphate R adjusted to pH 3 with phosphoric acid R, a suitable radioactivity detector, a loop injector, an internal recovery detection system, consisting of a loop of the chromatographic tubing between the injector and the column through the radioactivity detector, which has been calibrated for count recovery, maintaining the column at a constant temperature between 20 C and 30 C. Inject the test solution. Continue the chromatography for 10 min. In the chromatogram obtained, the first peak corresponds to the injected radioactivity of the test solution, the second peak corresponds to the amount of radioactivity as [15O]water. Calculate the percentage content of [15O]water from the areas of the peaks in the chromatogram obtained with the test solution. Not less than 99 per cent of the total radioactivity injected corresponds to oxygen-15 in the form of water. The injection may be released for use before completion of the test. RADIOACTIVITY Measure the radioactivity using suitable equipment by comparison with a standardised fluorine-18 solution or by using an instrument calibrated with the aid of such a solution. General Notices (1) apply to all monographs and other texts

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XENON (133Xe) INJECTION Xenoni (133Xe) solutio iniectabilis

DEFINITION Xenon (133Xe) injection is a sterile solution of xenon-133 that may be made isotonic by the addition of sodium chloride. Xenon-133 is a radioactive isotope of xenon and is obtained by separation from the other products of uranium fission. The injection contains not less than 80 per cent and not more than 130 per cent of the declared xenon-133 radioactivity at the date and hour stated on the label. The injection is presented in a container that allows the contents to be removed without introducing air bubbles. The container is filled as completely as possible and any gas bubble present does not occupy more than 1 per cent of the volume of the injection as judged by visual comparison with a suitable standard. CHARACTERS A clear, colourless solution. Xenon-133 has a half-life of 5.29 days and emits beta and gamma radiation and X-rays. IDENTIFICATION Record the gamma-ray and X-ray spectrum using a suitable instrument. The spectrum does not differ significantly from that of a standardised xenon-133 solution in a 9 g/l solution of sodium chloride R, apart from any differences attributable to the presence of xenon-131m and xenon-133m. If standardised xenon-133 solutions are not readily available, suitable standardised ionisation chambers are obtainable from laboratories recognised by the relevant competent authority. The most prominent gamma photon of xenon-133 has an energy of 0.081 MeV and there is an X-ray (resulting from internal conversion) of 0.030 MeV to 0.035 MeV. Xenon-131m has a half-life of 11.9 days and emits a gamma photon of 0.164 MeV. Xenon-133m has a half-life of 2.19 days and emits a gamma photon of 0.233 MeV. TESTS pH (2.2.3). The pH of the injection is 5.0 to 8.0. Sterility. It complies with the test for sterility prescribed in the monograph on Radiopharmaceutical preparations (0125). The injection may be released for use before completion of the test. RADIONUCLIDIC PURITY (a) Record the gamma-ray and X-ray spectrum using a suitable instrument. The spectrum does not differ significantly from that of a standardised xenon-133 solution in a 9 g/l solution of sodium chloride R, apart from any differences attributable to the presence of xenon-131m and xenon-133m. (b) Transfer 2 ml of the injection to an open flask and pass a current of air through the solution for 30 min, taking suitable precautions concerning the dispersion of radioactivity. Measure the residual beta and gamma activity of the solution. The activity does not differ significantly from the background activity detected by the instrument. RADIOACTIVITY Weigh the container with its contents. Determine its total radioactivity using suitable counting equipment by comparison with a standardised xenon-133 solution or by measurement in an instrument calibrated with the aid of such a solution, operating in strictly identical conditions. If an ionisation chamber is used its inner wall should be such 869

Xenon (133Xe) injection

EUROPEAN PHARMACOPOEIA 5.0

that the radiation is not seriously attenuated. Remove at least half the contents and re-weigh the container. Measure the radioactivity of the container and the remaining contents as described above. From the measurements, calculate the radioactive concentration of xenon-133 in the injection.

CAUTION Significant amounts of xenon-133 may be present in the closures and on the walls of the container. This must be taken into account in applying the rules concerning the transport and storage of radioactive substances and in disposing of used containers

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See the information section on general monographs (cover pages)