SPECIFIC MONOGRAPH TECHNETIUM ( 99M TC) SUCCIMER INJECTION

Transcription

1 SPECIFIC MONOGRAPH TECHNETIUM ( 99M TC) SUCCIMER INJECTION Dr Thomas Rühl RFC & MPharm Aljosa Stankovic University Hospital Clinical Center Banja Luka Thursday, September 10,

2 European Pharmacopoeia (PhEur) PhEur is a single reference work for the quality control of medicines in the member states of the PhEur Convention and the EU. 2

3 PhEur 8 th Edition Content 00 Introduction 01 General notices 02 Methods of Analysis (ph (2.2.3), UV/VIS (2.2.25), TLC (2.2.27), Sterility (2.6.1), Bacterial endotoxins (2.6.14), ) 03 Materials and Containers 04 Reagents (glacial acetic acid R , ) 05 General texts (Table of physical characteristics of radionuclides (5.07), ) 06 General monographs (Radiopharmaceutical preparations (0125),...) 07 Dosage Forms 08 Vaccines 09 Immunosera 10 Radiopharmaceutical preparations (TECHNETIUM ( 99m Tc) SUCCIMER INJECTION (0643), ) 11 Sutures 12 Herbal Drugs 13 Homeopathic preparations 14 to 17 Monographs A-Z (ACETIC ACID, GLACIAL (0590), ) 18 Index 3

4 Specific monographs Radiopharmaceutical preparations DEFINITION (all) PRODUCTION CHARACTERS (all) IDENTIFICATION (all) TESTS (all) RADIOACTIVITY (all) STORAGE LABELLING IMPURITIES (trend) 4

5 DEFINITION Sterile solution of a complex of technetium-99m with meso-2,3-dimercaptosuccinic acid. It is prepared using Sodium pertechnetate [ 99m Tc] injection (fission or non fission) (0124 or 0283). It contains: reducing substance (tin salt) stabilizers, antioxidants (ascorbic acid) inert additives Technetium-99m: 90 per cent to 110 per cent of the declared technetium-99m radioactivity at the date and time stated on the label. 99 Mo/ 99m Tc Generator 235 U(n,f)FP 99 Mo 99m Tc 99 Ru 98 Mo(n,γ) 99 Mo 99m Tc 99 Ru 5

6 CHARACTERS Appearance: clear, colourless solution.* Half-life and nature of radiation of technetium-99m: (5.7. Table of physical characteristics of radionuclides) *1.4 General Notice on Monographs: The statements under the heading Characters are not to be interpreted in a strict sense and are not requirements. 6

7 IDENTIFICATION A. Gamma-ray spectrometry. Result: technetium-99m (0.141 MeV) B. Chromatogram for radiochemical purity (Tests). Result: retardation factor radiochromatogram (R f : 0.0 to 0.1) C.*Place 1 ml of the preparation to be examined in a test-tube and add 0.1 ml of glacial acetic acid R and 1 ml of a 20 g/l solution of sodium nitroprusside R. Mix. Carefully place a layer of concentrated ammonia R at the top of the solution. A violet ring develops between the layers. RS - + [ Fe ( CN)5 NO ] 2- ( NH 3 ( a q)) [Fe ( CN)5 NOSR ] 3- * Berg et al. (1988) J. Clin, Chem. Clin. Biochem. 26,

8 TESTS ph (2.2.3): 2.3 to 3.5. Tin: maximum 1 mg/ml. Test solution. Dilute 1.5 ml of the preparation to be examined to 25.0 ml 103 g/l solution of hydrochloric acid R. Reference solution: g of stannous chloride R in a 103 g/l solution of hydrochloric acid R and dilute to ml. 1.0 ml of each solution add thioglycollic acid R, dithiol reagent R, 20 g/l solution of sodium laurilsulfate R and 21 g/l solution of hydrochloric acid R. Mix. Stand for 60 min. Measure the absorbance ((UV/VIS)2.2.25) of each solution at 540 nm (21 g/l solution of hydrochloric acid R as the compensation liquid) The absorbance of the test solution is not greater than that of the reference solution. 8

9 TESTS Physiological distribution. Inject a volume (0.2 ml) and containing not more than 0.1 mg of dimercaptosuccinic acid into a suitable vein (caudal vein) 3 rats each weighing g Measure the radioactivity in the syringe before and after the injection. Euthanise the rats 1 h after the injection. Remove the kidneys, the liver, the stomach, the lungs and, the tail (caudal vein) Determine the percentage of radioactivity In not fewer than 2 of the 3 rats used, the radioactivity is: - in the kidneys: minimum 40 per cent: - in the liver: maximum 10.0 per cent; - in the lungs: maximum 5.0 per cent; - in the stornach: maximum 2.0 per cent. 9

10 TESTS Sterility. It complies with the test for sterility prescribed in the monograph Radiopharmaceutical preparations (0125) membrane filtration The preparation may be released for use before completion of the test. 10

11 RADIOCHEMICAL PURITY Impurity A. Thin-layer chromatography (2.2.27). Plate: TLC silicagel plate R; use silica gel plate as the coating substance on a glass-fibre sheet, heated at 110 C for 10 min. Mobilephase: methyl ethyl ketone R. Application: 5-10 µl Development: immediately, over a path of cm (10 min) Drying: in air Detection: suitable detector R f values: [ 99m Tc]technetium succimer = 0.0 to 0.1; impurity A = 0.9 to 1.0. Limits: - [ 99m Tc]technetium succimer: minimum 95.0% - impurity A: maximum 2.0% 11

12 RADIOACTIVITY Determine the radioactivity using a calibrated instrument 12

13 STORAGE Protected from light 13

14 IMPURITIES IMPURITY A. [ 99m Tc]pertechnetate ion 14

15 THANK YOU FOR YOUR ATTENTION!!!! 15