Xenon (133Xe) injection EUROPEAN PHARMACOPOEIA 11.

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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EUROPEAN PHARMACOPOEIA 11.0
PRODUCTION
Alpha-emitting impurities : maximum 1 × 10-5 per cent of
the total radioactivity, determined on the parent radionuclide
strontium-90 by a suitable, validated method.
CHARACTERS
Appearance : clear, colourless solution.
Half-life and nature of radiation of yttrium-90 : see general
chapter 5.7. Table of physical characteristics of radionuclides.
IDENTIFICATION
A. Beta-particle spectrometry.
Result : the beta-particle spectrum obtained with the
preparation to be examined is qualitatively similar to the
beta-particle spectrum obtained with a certified yttrium-90
reference material.
B. pH (see Tests).
C. To 100 μL of silver nitrate solution R2 add 50 μL of the
preparation to be examined. A white precipitate is formed.
D. Examine the chromatograms obtained in the test for
radiochemical purity.
Result : the retardation factor of the principal peak in the
chromatogram obtained with the test solution is 0.4 to 0.7.
TESTS
pH (2.2.4): 1 to 2.
Cadmium (2.4.20) : maximum 0.6 μg/GBq.
Copper (2.4.20): maximum 0.6 μg/GBq.
Iron (2.4.20) : maximum 6.0 μg/GBq.
Lead (2.4.20) : maximum 3.0 μg/GBq.
Zinc (2.4.20) : maximum 3.0 μg/GBq.
Sterility. It complies with the test for sterility prescribed in
the monograph Radiopharmaceutical preparations (0125).
The preparation may be released for use before completion
of the test.
Bacterial endotoxins (2.6.14): less than 25 IU/mL, if intended
for use in the manufacture of parenteral preparations without
a further appropriate procedure for the removal of bacterial
endotoxins.
RADIONUCLIDIC PURITY
The preparation may be released for use before completion of
test B for yttrium-90.
Strontium-90. Beta-particle spectrometry (2.2.66).
Limit : maximum 0.002 per cent of the total yttrium-90
radioactivity.
Determine the relative amount of strontium-90 after its
separation from the examined sample of the preparation to
be examined.
Soak 100 mg of extraction resin R (50-100 μm) in 1 mL of
a 94.7 g/L solution of nitric acid R for at least 24 h. Stir the
resin suspension for 10 min using a magnetic stirrer at about
800 r/min. Into a polypropylene column with a suitable bed
support at the bottom, introduce 1 mL of the resin suspension.
Cover the resin in the column with another bed support. Keep
the resin bed covered with a 94.7 g/L solution of nitric acid R
and free from air bubbles.
Test solution. Add a volume of the preparation to be examined
corresponding to 100-200 MBq to 4 mL of a 100 mg/mL
solution of strontium chloride hexahydrate R in a 474 g/L
solution of nitric acid R. Measure the radioactivity of
this solution using a calibrated instrument. Add 50 μL of
strontium-85 spiking solution R and mix.
Reference solution. Mix 50 μL of strontium-85 spiking
solution R and 2.5 mL of a 9.5 g/L solution of nitric acid R in a
vial for liquid scintillation counting and add 10 mL of liquid
scintillation cocktail R.
General Notices (1) apply to all monographs and other texts
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Yttrium ( 90Y) chloride solution for radiolabelling
Condition the extraction resin column with 2 mL of a 474 g/L
solution of nitric acid R. Apply the test solution to the top
of the column. Collect the eluate in a tared vial. Rinse the
column with 4 mL of a 474 g/L solution of nitric acid R and
collect the eluate in the tared vial. Perform the elutions of the
column at a flow rate not exceeding 1 mL/min (0.6 mL/min is
recommended). Combine the eluates and weigh the resulting
mixture.
Transfer 1 mL of the eluate to a vial for liquid scintillation
counting and determine the mass of the sample, then add
1.5 mL of water R and 10 mL of liquid scintillation cocktail R
and mix (eluate mixture).
Within 20 min following collection of the eluate determine
the total radioactivity due to strontium-90, yttrium-90
and strontium-85 in the eluate mixture and in the
reference solution by liquid scintillation spectrometry. The
recommended counting time is 900 s.
Calculate the recovery of strontium-85 in the eluate mixture.
Calculate the total radioactivity due to strontium-90 and
yttrium-90 in the eluate, taking into account the recovery of
strontium and the fraction of eluate in the eluate mixture.
System suitability :
– the radioactivity due to yttrium-90 in the eluate does not
exceed 50 per cent of the radioactivity due to strontium-90.
Yttrium-90 : minimum 99.9 per cent of the total radioactivity.
A. Gamma-ray-emitting impurities. Gamma-ray
spectrometry. Preliminary test.
Place a volume of the preparation to be examined
corresponding to about 200 MBq in a glass vial and
measure the radioactivity in an ionisation chamber.
Place the vial in a lead container with 10 mm-thick walls.
Place the lead container in a gamma-spectrometer chamber
and perform the measurement with the acquisition time
set to 3600 s.
If any impurities are detected, calculate their radioactivities
corrected to correspond to the time that the radioactivity
of the sample of the preparation to be examined was
measured. Calculate the relative impurity content in the
sample of the preparation to be examined.
B. Gamma-ray-emitting impurities. Gamma-ray
spectrometry.
Determine the relative amounts of gamma-ray-emitting
impurities present. For the detection and quantification of
gamma-ray-emitting impurities, retain the preparation to
be examined for a sufficient time to allow yttrium-90 to
decay to a level that permits the detection of radionuclidic
impurities.
Result : the total radioactivity due to radionuclidic
impurities is not greater than 0.1 per cent.
RADIOCHEMICAL PURITY
Yttrium in the form of Y3+ ion. Thin-layer chromatography
(2.2.27).
Test solution. The preparation to be examined.
Reference solution. To 1.0 mL of the test solution add 0.4 mL
of a 10 g/L solution of pentetic acid R in a 4 g/L solution of
sodium hydroxide R.
Plate : TLC silica gel plate R ; use a glass-fibre plate.
Mobile phase : 9.0 g/L solution of sodium chloride R adjusted
to pH 2.3 ± 0.05 with dilute hydrochloric acid R.
Application : 5 μL.
Development : immediately, over 2/3 of the plate.
Drying : in a current of cold air.
Detection : suitable detector to determine the distribution of
radioactivity.
Retardation factors : impurity B = less than 0.2 ; yttrium-90
in the form of Y3+ ion = 0.4 to 0.7 ; yttrium-90 in the form of
yttrium pentetate = greater than 0.9.
1335
Yttrium (90Y) chloride solution for radiolabelling EUROPEAN PHARMACOPOEIA 11.0

System suitability : the retardation factor of the principal peak – the concentration of hydrochloric acid ;
in the radiochromatogram obtained with the test solution – the content of cadmium, copper, iron, lead, zinc and
is clearly different from that of the principal peak in the strontium-90 ;
chromatogram obtained with the reference solution.
– that it is the user’s obligation to verify that the content of
Limit : metal impurities and strontium-90 is sufficiently low for
– yttrium in the form of Y3+ ion : minimum 99 per cent of the the intended application ;
total radioactivity due to yttrium-90.
– that the solution is intended for use in the preparation of
RADIOACTIVITY yttrium-90-labelled radiopharmaceuticals.
Determine the radioactivity using a calibrated instrument. IMPURITIES
LABELLING
A. strontium-90,
The label states :
– that the solution is not for direct administration to humans ; B. yttrium-90 in colloidal form.

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