EUROPEAN PHARMACOPOEIA 10.

5 PSMA-1007 (18F) injection

07/2021:3116 Reference solution (a) : water R.

PSMA-1007 (18F) INJECTION
PSMA-1007 (18F) solutio iniectabilis
C49H5518FN8O16 Mr 1030
[2093321-19-6]
DEFINITION
Sterile solution of (3S,10S,14S)-1-[4-[[(2S)-4-carboxy-
2-[(2S)-4-carboxy-2-(6-[18F]fluoropyridin-3-
amido)butanamido]butanamido]methyl]phenyl]-3-
[(naphthalen-2-yl)methyl]-1,4,12-trioxo-2,5,11,13-
tetraazahexadecane-10,14,16-tricarboxylic acid
([18F]PSMA-1007). It may contain stabilisers such as ascorbic (2.2.29).
acid.
This monograph applies to an injection containing
[18F]PSMA-1007 produced by nucleophilic substitution.
Content :
– fluorine-18 : 90 per cent to 110 per cent of the declared
fluorine-18 radioactivity at the date and time stated on the 30 mL of the solution with 10 mL of the solvent mixture.
label ;
– PSMA-1007 : maximum 0.1 mg per maximum
recommended dose in millilitres.
CHARACTERS
Appearance : clear, colourless or slightly yellow solution.
Half-life and nature of radiation of fluorine-18 : see general
chapter 5.7. Table of physical characteristics of radionuclides. If necessary, add 1 mL of water R so that the solution is no
IDENTIFICATION
A. Gamma-ray spectrometry.
Result : the principal gamma photons have an energy of
0.511 MeV and, depending on the measurement geometry, impurity D) in 4 mL of anhydrous ethanol R. If necessary, add
a sum peak of 1.022 MeV may be observed.
B. Approximate half-life : 105 min to 115 min.
C. Examine the chromatograms obtained in the test for other Reference solution (d). To 1 mL of reference solution (b) add
radiochemical impurities under Radiochemical purity (see 1 mL of reference solution (c) and dilute to 10 mL with the
Tests).
Result : the principal peak in the radiochromatogram
obtained with the test solution is similar in retention time
to the principal peak in the chromatogram obtained with
reference solution (a).
TESTS
pH (2.2.4) : 4.5 to 8.5.
Impurity A (tetrabutylammonium) (2.4.33). It complies
with the test.
Impurity E. Spot test.
Test solution. To 100 μL of the preparation to be examined
add 400 μL of water R and mix.
Reference solution (b). Dissolve 11.0 mg of aminopolyether R
(impurity E) in water R and dilute to 25.0 mL with the same
solvent. Dilute 1.0 mL of the solution to V with water R, V
being the maximum recommended dose in millilitres.
Plate : TLC silica gel plate for aminopolyether test R.
Application : 2.5 μL ; as an additional spot, apply 2.5 μL of the
test solution and then 2.5 μL of reference solution (b) at the
same place.
Detection : visually compare the spots 1 min after application.
System suitability :
– the spot due to the application of both the test solution
and reference solution (b) is similar in appearance to the
spot due to reference solution (b), which is characterised
by a number of concentric circles ; the darker innermost
circle (of intensity proportional to the concentration
of impurity E) may be surrounded by a bluish-black
ring, outside of which is a lighter circle surrounded by a
peripheral dark edge ;
– the spot due to reference solution (a) has a more diffuse
inner circle, which is brownish-pink and without a distinct
margin between it and the surrounding lighter zone ;
– the spot due to reference solution (b) is clearly different
from the spot due to reference solution (a).
Limit :
– the central portion of the spot due to the test solution is
not more intense than that of the spot due to reference
solution (b) (2.2 mg/V).
PSMA-1007 and related substances. Liquid chromatography
Solvent mixture : anhydrous ethanol R, water R (40:60 V/V).
Solution A. Dissolve 20 mg of potassium chloride R, 0.80 g of
sodium chloride R, 20 mg of potassium dihydrogen phosphate R
and 0.114 g of anhydrous disodium hydrogen phosphate R in
water R and dilute to 100 mL with the same solvent. Mix
Test solution. The preparation to be examined.
Reference solution (a). To 1.0 mg of PSMA-1007 R add 5 mL
of solution A, sonicate for 5 min and dilute to 10.0 mL with
solution A. Dilute 1.0 mL of the solution to V with solution A,
V being the maximum recommended dose in millilitres.
Reference solution (b). Dissolve 1 mg of defluorohydroxy-
PSMA-1007 R (impurity C) in 4 mL of anhydrous ethanol R.
longer opalescent. Sonicate for 5 min and dilute to 10 mL
with water R.
Reference solution (c). Dissolve 1 mg of defluorotrimethylami-
nium-PSMA-1007 trifluoroacetate R (trifluoroacetate salt of
1 mL of water R so that the solution is no longer opalescent.
Sonicate for 5 min and dilute to 10 mL with water R.
solvent mixture.
Column :
– size : l = 0.15 m, Ø = 4.6 mm ;
– stationary phase : solid core octadecylsilyl silica gel for
chromatography R (2.7 μm);
– temperature : 30 °C.
Mobile phase :
– mobile phase A : to 1000 mL of a 3.12 g/L solution of
sodium dihydrogen phosphate R add 10.0 mL of a 90 g/L
solution of phosphoric acid R and adjust to pH 2.5 ± 0.1
with phosphoric acid R ;
– mobile phase B : acetonitrile for chromatography R ;

General Notices (1) apply to all monographs and other texts 5725
PSMA-1007 (18F) injection EUROPEAN PHARMACOPOEIA 10.5

Time Mobile phase A Mobile phase B Result : the total radioactivity due to radionuclidic
(min) (per cent  V/V) (per cent  V/V) impurities is not more than 0.1 per cent.
0-2 77 23
RADIOCHEMICAL PURITY
2 - 14 77 → 70 23 → 30 [18F]PSMA-1007 : minimum 91 per cent of the total
14 - 17 70 → 40 30 → 60 radioactivity due to fluorine-18.
17 - 21 40 60 Impurity B. Thin-layer chromatography (2.2.27).
Test solution : The preparation to be examined.
Flow rate : 1.3 mL/min.
Plate : TLC silica gel plate R.
Detection : spectrophotometer at 225 nm and radioactivity
detector connected in series. Mobile phase : water R, acetonitrile R (40:60 V/V).
Injection : 20 μL. Application : about 2 μL.
Relative retention with reference to PSMA-1007 Development : over 2/3 of the plate.
(retention time = about 11 min) : impurity D = about 0.5 ;
impurity C = about 0.6. Drying : in a current of warm air.

System suitability : reference solution (d) using the Detection : suitable detector to determine the distribution of
spectrophotometer : radioactivity.

– resolution : minimum 2.0 between the peaks due to
impurities D and C.
Limits : in the chromatogram obtained with the
spectrophotometer :
– PSMA-1007 : not more than the area of the corresponding
peak in the chromatogram obtained with reference
solution (a) (0.1 mg/V) ;
– any other impurity : for each impurity, not more than the
area of the principal peak in the chromatogram obtained
with reference solution (a) (0.1 mg/V);
– total : not more than 5 times the area of the principal peak
in the chromatogram obtained with reference solution (a)
(0.5 mg/V) ;
– disregard limit : 0.3 times the area of the principal peak in
the chromatogram obtained with reference solution (a)
(0.03 mg/V).
Residual solvents : limited according to the principles defined
in general chapter 5.4. The preparation may be released for
use before completion of the test.
Ethanol (2.4.24 or another suitable, validated method) :
maximum 10 per cent V/V and maximum 2.5 g per
administration, taking the density (2.2.5) to be 0.790 g/mL.
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 175/V IU/mL, V
being the maximum recommended dose in millilitres. The
preparation may be released for use before completion of the
test.
RADIONUCLIDIC PURITY
The preparation may be released for use before completion of
test B.
Fluorine-18 : minimum 99.9 per cent of the total radioactivity. LABELLING
A. Gamma-ray spectrometry.
Limit : peaks in the gamma-ray spectrum corresponding
to photons with an energy different from 0.511 MeV or
1.022 MeV represent not more than 0.1 per cent of the total IMPURITIES
radioactivity.
B. Gamma-ray spectrometry.
Determine the amount of fluorine-18 and radionuclidic
impurities with a half-life longer than 2 h. For the detection the tests in the monograph. They are limited by the general
and quantification of impurities, retain the preparation to
be examined for at least 24 h to allow the fluorine-18 to
decay to a level that permits the detection of impurities.
Retardation factors : impurity B = about 0 ; [18F]PSMA-
1007 = about 0.7.
Limit :
– impurity B : maximum 5 per cent of the total radioactivity
due to fluorine-18.
Other radiochemical impurities. Liquid chromatography
(2.2.29) as described in the test for PSMA-1007 and related
substances. If necessary, dilute the test solution with
solution A to obtain a radioactivity concentration suitable for
the radioactivity detector.
Examine the chromatogram recorded using the radioactivity
detector and locate the peak due to [18F]PSMA-1007 by
comparison with the chromatogram obtained with reference
solution (a) using the spectrophotometer.
Calculate the total amount of [18F]PSMA-1007 of the
preparation using the following expression :
(100 - B) ´ T
B  =  percentage of radioactivity due to impurity B
determined in the test for impurity B under
Radiochemical purity ;
T  =  proportion of the radioactivity in the peak due
to [18F]PSMA-1007 relative to the total eluted
radioactivity in the chromatogram obtained with
the test solution in the liquid chromatography test
for other radiochemical impurities. Disregard any
peak with a relative retention with reference to
PSMA-1007 of 0.8 or less.
RADIOACTIVITY
Determine the radioactivity using a calibrated instrument.
The label states the percentage content of ethanol in the
preparation.
Specified impurities : A, B, E.
Other detectable impurities (the following substances would,
if present at a sufficient level, be detected by one or other of
acceptance criterion for other/unspecified impurities. It
is therefore not necessary to identify these impurities for
demonstration of compliance) : C, D.

5726 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.5 PSMA-1007 (18F) injection

A. N,N,N-tributylbutan-1-aminium (tetrabutylammonium),

B. [18F]fluoride,

D. 5-[[(2S)-4-carboxy-1-[[(2S)-4-carboxy-1-[[[4-
[(3S,10S,14S)-10,14-dicarboxy-17-hydroxy-3-[(naphtha-
len-2-yl)methyl]-1,4,12,17-tetraoxo-2,5,11,13-tetraazahep-
tadecan-1-yl]phenyl]methyl]amino]-1-oxobutan-2-yl]ami-
no]-1-oxobutan-2-yl]carbamoyl]-N,N,N-trimethylpyri-
din-2-aminium (defluorotrimethylaminium-PSMA-1007),

C. (3S,10S,14S)-1-[4-[[(2S)-4-carboxy-2-[(2S)-4-car-
boxy-2-(6-hydroxypyridin-3-amido)butanami-
do]butanamido]methyl]phenyl]-3-[(naphtha-
len-2-yl)methyl]-1,4,12-trioxo-2,5,11,13-tetraaza-
hexadecane-10,14,16-tricarboxylic acid (defluorohy- E. 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]­hexaco-
droxy-PSMA-1007), sane (aminopolyether).

General Notices (1) apply to all monographs and other texts 5727