EUROPEAN PHARMACOPOEIA 11.

0 Water (15O) injection

IDENTIFICATION 01/2008:1582
corrected 7.0
Beta-ray spectrometry as described in test A for radionuclidic
purity (see Tests).
Result : the maximum energy of the beta radiation is
0.019 MeV.
WATER (15O) INJECTION
TESTS
pH (2.2.3) : 4.5 to 7.0. Aquae (15O) solutio iniectabilis
Sterility. It complies with the test for sterility prescribed in DEFINITION
the monograph Radiopharmaceutical preparations (0125). Sterile solution of [15O]water for diagnostic use.
RADIONUCLIDIC PURITY Oxygen-15 : 90 per cent to 110 per cent of the declared
A. Test solution. Mix 100 μL of a suitable dilution of oxygen-15 radioactivity at the date and time stated on the
the preparation to be examined with 10 mL of liquid label.
scintillation cocktail R1. CHARACTERS
Reference solution. A standardised tritiated (3H) water Appearance : clear, colourless liquid.
having approximately the same radioactivity as the test Half-life and nature of radiation of oxygen-15 : see general
solution. chapter 5.7. Table of physical characteristics of radionuclides.
Measure the radioactivity of the test solution in a liquid IDENTIFICATION
scintillation counter fitted with a discriminator. The count
should be about 5000 impulses per second at the lowest A. Gamma-ray spectrometry.
setting of the discriminator. Record the count at different Results : the only gamma photons of [15O]water have an
discriminator settings. For each measurement, count energy of 0.511 MeV and, depending on the measurement
at least 10 000 impulses over a period of at least 1 min. geometry, a sum peak of 1.022 MeV may be observed.
Immediately determine in the same conditions the count B. Radionuclidic purity (see Tests).
for the reference solution. C. Examine the chromatogram obtained in the test for
Plot the counts at each discriminator setting, correcting radiochemical purity (see Tests). The retention time of
for background activity, on semi-logarithmic paper, the the 2nd peak is due to the radioactivity eluting in the
discriminator settings being in arbitrary units as the void volume.
abscissae. The vertical distance between the 2 curves TESTS
obtained is constant. They obey the following mathematical
relationship : pH (2.2.3) : 5.5 to 8.5.
Ammonium (2.4.1): maximum 10 ppm, determined on 1 mL.
A1 A2 The preparation may be released for use before completion
-
B1 B2 of the test.
´ 100 < 20
A1 Nitrates : maximum 10 ppm. The preparation may be released
B1 for use before completion of the test.
Test solution. To 1 mL add 49 mL of nitrate-free water R. Place
A1 = radioactivity recorded for the reference solution 5 mL of this solution in a test-tube immersed in iced water, add
at the lowest discriminator setting ; 0.4 mL of a 100 g/L solution of potassium chloride R, 0.1 mL of
B1 = radioactivity recorded for the test solution at the diphenylamine solution R and, dropwise with shaking, 5 mL of
lowest discriminator setting ; sulfuric acid R. Transfer the tube to a water-bath at 50 °C.
A2 = radioactivity recorded for the reference Reference solution. Prepare at the same time in the same
solution at the discriminator setting such that manner as the test solution, using a mixture of 4.5 mL of
A 2 » A1 ´ 10-3 ; nitrate-free water R and 0.5 mL of nitrate standard solution
B2 = radioactivity recorded for the test solution at the (2 ppm NO3) R.
latter discriminator setting. After 15 min, any blue colour in the test solution is not more
intense than that in the reference solution.
B. Gamma-ray spectrometry. The instrument registers only
background activity. Sterility. It complies with the test for sterility prescribed in
the monograph Radiopharmaceutical preparations (0125).
RADIOCHEMICAL PURITY The preparation may be released for use before completion
Place a quantity of the preparation to be examined equivalent of the test.
to about 74 kBq, diluted to 50 mL with water R, in an all-glass Bacterial endotoxins (2.6.14) : less than 175/V IU/mL, V
distillation apparatus of the type used for the determination being the maximum recommended dose in millilitres. The
of distillation range (2.2.11). Determine the radioactive preparation may be released for use before completion of the
concentration. Distil until about 25 mL of distillate has been test.
collected. Precautions must be taken to avoid contamination
of the air. If the test is carried out in a fume cupboard, the RADIONUCLIDIC PURITY
equipment must be protected from draughts. Determine the The preparation may be released for use before completion
radioactive concentration of the distillate and of the liquid of the test.
remaining in the distillation flask. Neither of the radioactive Oxygen-15 : minimum 99 per cent of total radioactivity.
concentrations determined after distillation differs by more Gamma-ray spectrometry.
than 5 per cent from the value determined before distillation.
Results :
– the spectrum obtained with the preparation to be examined
RADIOACTIVITY does not differ significantly from that obtained with a
Determine the radioactivity using a liquid scintillation standardised fluorine-18 solution ;
counter. – the half-life is between 1.9 min and 2.2 min.

General Notices (1) apply to all monographs and other texts 1333
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Xenon (133Xe) injection EUROPEAN PHARMACOPOEIA 11.0

RADIOCHEMICAL PURITY TESTS

The preparation may be released for use before completion pH (2.2.3) : 5.0 to 8.0.
of the test.
Sterility. It complies with the test for sterility prescribed in
[ 15O]Water. Liquid chromatography (2.2.29). the monograph Radiopharmaceutical preparations (0125).
Test solution. The preparation to be examined. The preparation may be released for use before completion
Column : of the test.
– size : l = 0.25 m, Ø = 4.0 mm ; RADIONUCLIDIC PURITY
– stationary phase : aminopropylsilyl silica gel for A. Gamma-ray and X-ray spectrometry.
chromatography R (10 μm); Comparison : standardised xenon-133 solution in a 9 g/L
solution of sodium chloride R.
– temperature : constant, at 20-30 °C.
Result : the spectrum obtained with the preparation to be
Mobile phase : 10 g/L solution of potassium dihydrogen examined does not differ significantly from that obtained
phosphate R adjusted to pH 3 with phosphoric acid R. with a standardised xenon-133 solution in a 9 g/L solution
Flow rate : 1 mL/min. of sodium chloride R, apart from any differences attributable
Detection : suitable detector to determine the distribution to the presence of xenon-131m and xenon-133m.
of radioactivity and internal recovery detection system, B. Transfer 2 mL of the preparation to be examined to an
consisting of a loop of the chromatographic tubing between open flask and pass a current of air through the solution
the injector and the column through the radioactivity detector, for 30 min, taking suitable precautions concerning the
which has been calibrated for count recovery. dispersion of radioactivity. Measure the residual beta and
Run time : 10 min. gamma activity of the solution. The activity does not differ
Identification of peaks : in the chromatogram obtained with significantly from the background activity detected by the
the test solution, the 1st peak corresponds to the injected instrument.
radioactivity of the test solution, the 2nd peak corresponds toRADIOACTIVITY
the amount of radioactivity as [15O]water. Weigh the container with its contents. Determine its
Limit : total radioactivity using suitable counting equipment by
– [15O]water : minimum 99 per cent of the total radioactivity comparison with a standardised xenon-133 solution or by
due to oxygen-15. measurement in an instrument calibrated with the aid of such
a solution, operating in strictly identical conditions. If an
RADIOACTIVITY ionisation chamber is used its inner wall should be such that
Determine the radioactivity using a calibrated instrument. the radiation is not seriously attenuated. Remove at least half
the contents and re-weigh the container. Measure the total
residual radioactivity of the container and the remaining
contents as described above. From the measurements,
01/2008:0133 calculate the radioactive concentration of xenon-133 in the
corrected 7.0 preparation to be examined.

CAUTION
Significant amounts of xenon-133 may be present in the
closures and on the walls of the container. This must be taken
XENON (133Xe) INJECTION into account in applying the rules concerning the transport
and storage of radioactive substances and in disposing of used
containers
Xenoni (133Xe) solutio iniectabilis
IMPURITIES
DEFINITION A. xenon-131m.
Sterile solution of xenon-133 that may be made isotonic by the
addition of sodium chloride. 04/2019:2803
Xenon-133 : 80 per cent to 130 per cent of the declared
xenon-133 radioactivity at the date and time stated on the
label.
The injection is presented in a container that allows the
contents to be removed without introducing air bubbles. The YTTRIUM ( 90Y) CHLORIDE SOLUTION
container is filled as completely as possible and any gas bubble
present does not occupy more than 1 per cent of the volume FOR RADIOLABELLING
of the injection as judged by visual comparison with a suitable
standard. Yttrii (90Y) chloridi solutio ad
CHARACTERS radio-signandum
Appearance : clear, colourless solution. 90
YCl3 Mr 196.3
Half-life and nature of radiation of xenon-133 : see general [39271-65-3]
chapter 5.7. Table of physical characteristics of radionuclides.
DEFINITION
IDENTIFICATION
Sterile solution containing yttrium-90 derived from
Gamma-ray and X-ray spectrometry. fission-produced strontium-90, in the form of yttrium chloride
Comparison : standardised xenon-133 solution in a 9 g/L in dilute hydrochloric acid.
solution of sodium chloride R. Content :
Results : the most prominent gamma photon of xenon-133 has – yttrium-90 : 90 per cent to 110 per cent of the declared
an energy of 0.081 MeV and there is an X-ray (resulting from yttrium-90 radioactivity at the date and time stated on the
internal conversion) of 0.030 MeV to 0.035 MeV. label.

1334 See the information section on general monographs (cover pages)

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