Working document QAS/09.301 rev
September 2009
RESTRICTED
SAMARII (
153
Sm) ETHYLENI DIAMINI TETRAMETHYLENI
PHOSPHONATIS MULTIPLEX (EDTMP) INJECTIO
SAMARIUM (
153
Sm) ETHYLENEDIAMINE TETRAMETHYLENE
PHOSPHONATE (EDTMP) COMPLEX INJECTION
Other name. (
153
Sm)-EDTMP injection.
Description. Samarium (
153
Sm) ethylenediamine tetramethylene phosphonate injection is
a clear colourless solution.
Samarium-153 has a half-life of 46.3 hours.
Category. Therapeutic.
Storage. Samarium (
153
Sm) ethylenediamine tetramethylene phosphonate injection
should be kept at a temperature between 2°C to 8°C, protected from light and during
transportation, at a temperature below -10°C.
After aseptic withdrawal of the first dose from a multidose container, the container
should be stored at a temperature between 2°C to 8°C and the contents used within 7
days.
Labelling. State the date of withdrawal of the first dose for multidose containers.
Additional information. Wherever V is used within the tests of this monograph, V is the
maximum recommended dose in millilitres.
Requirements
Complies with the monograph for “Parenteral Preparations” and with that for
“Radiopharmaceuticals”.
Definition. Samarium (
153
Sm ) ethylenediamine tetramethylene phosphonate injection is
a sterile solution of samarium-153 complexed with ethylenediamine tetramethylene
phosphonate (EDTMP) present in excess. The injection is suitable for intravenous
administration and contains sufficient sodium chloride to make the solution isotonic with
Working document QAS/09.301 rev
page 2
blood. (
153
Sm)-EDTMP injection contains not less than 90% and not more than 110% of
the content of samarium-153 stated on the label at the reference date and time stated on
the label. Not less than 99.8% of the total radioactivity is due to samarium-153. Not less
than 95% of the total samarium-153 radioactivity is present as EDTMP complex.
Manufacture
Radionuclide production. Samarium-153 may be obtained by neutron irradiation of
enriched samarium oxide (
152
Sm) Sm
2
O
3
in quartz ampoule.
Production of radiopharmaceutical preparation. Samarium (
153
Sm) chloride is
complexed by addition to a solution of EDTMP that is present in excess. EDTMP may be
previously synthesized from phosphorous acid, ethylenediamine and formaldehyde using
the Mannich-type reaction. It is then purified by successive re-crystallizations and
identified by infrared spectroscopy. The pH of the stock solution of EDTMP in sodium
hydroxide is adjusted to 7-7.5 for complexation with samarium-153. (
153
Sm)-EDTMP
injection may contain stabilizing agents as well as buffers and it may be sterilized by
"Heating in an autoclave" (see 5.8 Methods of sterilization).
Identity tests
•
Either tests A and C or tests B and C may be applied.
A.
Record the gamma-ray and X-ray spectra using a suitable instrument with a sample
of samarium-153, suitably diluted if needed. The spectrum is concordant with the
reference spectrum
of a specimen of samarium-153 in that it exhibits major peaks
of 70 and 103 keV.
Standardized samarium-153 solutions are available from laboratories recognized by
the relevant national or regional authority.
B.
The half-life determined using a suitable detector system is between 44 and 49
hours.
C.
Examine the radiochromatogram obtained in the test for radiochemical purity. The
distribution of the radioactivity contributes to the identification of the preparation.
pH value. Carry out the test as described in the monograph for “Radiopharmaceuticals”.
pH of the injection, 7.0 to 8.5.
Sterility. The injection complies with 3.2 Test for sterility, modified as described in the
monograph for “Radiopharmaceuticals”. Test for sterility will be initiated on the day of
manufacture. The injection may be released for use before completion of the test.
Bacterial endotoxins. Carry out the test as described under 3.4 Test for bacterial
endotoxins, modified as described in the monograph for “Radiopharmaceuticals”. The
Working document QAS/09.301 rev
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injection contains not more than 175/V I.U. of endotoxins per millilitre. The injection
may be released for use before completion of the test.
Radionuclidic purity. Record the gamma-ray and X-ray spectrum using a suitable
instrument and measure the half-life using a suitable method. Determine the relative
amounts of samarium-153, europium-154 and other radionuclidic impurities that may be
present. Not less than 99.8% of the total radioactivity is due to samarium-153 and not
more than 0.01% of the total radioactivity is due to europium-154. The sum of all
gamma-emitting impurities is less than 0.2%.
Radiochemical purity. Carry out the test as described under 1.14.2 Paper
chromatography and ascending conditions, using cellulose paper strips
1
. Apply to the
paper about 5 µl of the injection to be examined, suitably diluted to give an optimum
count rate and develop for a distance of 20 cm with a mixture of 0.2 volumes of ammonia
(260 g/l) TS and 40 volumes of water R. Allow the paper to dry in air and determine the
radioactivity distribution by a suitable method. In this system, samarium-153 has an Rf
value of about 0 and the (
153
Sm)-EDTMP complex has an Rf value of about 0.6. Not less
than 95% of the total radioactivity is in the spot corresponding to the (
153
Sm)-EDTMP
complex.
Radioactivity. Determine the radioactivity in a suitable calibrated counting equipment by
comparison with a standardized samarium-153 solution or by measurement in an
instrument calibrated with the aid of such a solution.
Standardized samarium-153 solutions are available from laboratories recognized by the
relevant national or regional authority.
***
1
Whatman 1 or Whatman 3MM have been found to be suitable