VAEC-AR 06--33
STUDY ON ANALYTICAL METHODS OF TELLURIUM CONTENT IN NATRIIODIDE (Na131I) RADIOPHARMACEUTICAL SOLUTION PRODUCED IN THE DALAT NUCLEAR REACTOR Vo Thi Cam Hoa, Duong Van Dong, Nguyen Thi Thu, Chu Van Khoa, Bui Van Cuong, Mai Phuoc Tho, Pham Ngoc Dien and Nguyen Thanh Binh Nuclear Research Institute Abstract: This annual report describes the practical methods for analyzing of Tellurium content in Na131I solution produced at the Dalat Nuclear Research Institute. We studied analytical methods to control Tellurium content in final Na131I solution product used in medical purposes by three methods such as: spot test, gamma spectrometric and spectrophotometeric methods. These investigation results are shown that the spot test method is suitable for controlling Tellurium trace in the final product. This spot test can be determinate Tellurium trace less than 10 ppm and are used to quality control of Na131I solution using in medical application.
I. Introduction Na131I solution is prepared in the Center for Research and Ra®ioisotope Production by dry distillation method from irradiated Tellurium dioxide. This solution can be contaminated Tellurium while international pharmacopeias only accepted Tellurium content less than 10 ppm. For this reason, we have to study analytical methods to control Tellurium content in final Na131I solution product using in medical purposes produced at the Dalat Nuclear Research Institute by three methods that are spot test, gamma spectrometric and spectrophotometeric methods. II. The analysis methods 1. Determination of Tellurium in Na131I solution by spot test method a. Preparation of reagents: - Stannous chloride solution 5.0% (fresh preparation): Stannous chloride dehydrate (SnCl2.2H2O) 0.25 g is dissolved in 0.25ml of concentrated hydrochloric acid, heated to the clear solution and diluted to 5 ml with distilled water. - Sodium hydroxide solution 25.0%: Sodium hydroxide 25 g is dissolved in 100 ml of distilled water. - Standard Tellurium solution 10.0ppm: Stock solution of Tellurium 1,000 ppm is prepared by dissolving 125.0862 mg of Tellurium dioxide in 2.7 ml of 25% sodium hydroxide and to make the volume to 100 ml by distilled water. The stock solution is diluted with distilled water to prepare the standard solution with concentration 10.0 ppm. b. Chemical reaction: SnCl2 + NaOH (®Æc) = Na[Sn(OH)3] + 2NaCl Na2TeO3 + 2Na[Sn(OH)3] + 3H2O = Te↓ + 2Na2[Sn(OH)6] c. The optimal conditions of determination of Tellurium content by spot test method are investigated as below: The Annual Report for 2006, VAEC
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Concentration of stannous chloride solution was 5.0% Concentration of sodium hydroxide solution was 25.0% Reaction time was 10 minutes.
d. Procedure: - Place two drops (100 μl ) of standard Tellurium solution, water (blank) and sodium iodide (sample) solution into hole of spot plate. - Add two drops (100 μl ) of stannous chloride solution 5.0%, saturated sodium carbonate and 25% sodium hydroxide respectively. - Compare the black precipitation of Tellurium metal from the sample with standard Tellurium and blank samples (Te4+ is reduced by Sn2+ to give the black Tellurium metal). If there is preservative such as sodium thiosulfate (Na2S2O3) in the sample solution, it will give the dark brown precipitation together with Tellurium metal. 2. Determination of Tellurium in Na131I solution by gamma- spectrometric method a. Preparation of reagents: CCl4 solvent (p.A); HNO3 (7N); KI 1mg/ml; Standard Tellurium solution 10.0ppm. Target preparation: Tellurium standard was prepared by taking 0.12508 g TeO2 (p.A) in quartz ampoule. The Tellurium standard and production target in reactor irradiation container were irradiated on the reactor in the similar irradiation conditions with Thermal neutron flux was 2.1013 n.cm-2.s-1, irradiation time was 108 h, cooling time was 48 h and irradiation position: neutron trap. The ampoule containing Tellurium standard was taken in a beaker containing 2ml NaOH 25%, followed by bidistiled water to make the volume to 100 ml. Its stock standard solution Te 1mg/ml. The stock solution is diluted with distilled water to prepare the standard solution with concentration 10.0 ppm. Instrumentation: gamma-ray emitters were counted on a gamma-ray spectrometer MAN–GMX-PTN INAA in conjunction with semiconductor detector GMX-30190 (ORTEC). Measurement and spectrum were processed by Gamma Vision 32 (ORTEC) calibrated energy, efficacy and calculated by relative method. b. Extraction of iodine with tetracarbonchloride: Tetracarbonchloride is found to be useful extractant for iodine in nitric acid. The formation of I2 is described as follows: 2NaI +
4HNO3
=
I2 + 2NO2 + 2NaNO3 + 2 H2O
Tetracarbonchloride used was analytical grade or chemically pure as necessary. The initial Tellurium concentration in Na131I was too small in the aqueous phase. The addition of KI carrier is necessary to avoid ultra-dilution phenomenon. We have studied optimal conditions for the iodine extraction and extraction procedure such as carrier content, acid concentration and effect of iodine concentration, reaction time and number of extraction times. Our optimal extraction procedure was given as follows: Two and half ml of bidistilled water and 100μl of Na131I solution were transferred into a separatory funnel of 60 ml volume. 100 μl solution of KI 1mg/ml as the carrier were added, 2ml of HNO3 7N were added, followed by drop by drop
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(∼300μl) of concentrated nitric acid into the funnel. The mixture is mixed well until formation of the color solution and standed for 2 minutes (I- is oxidized to give I2). Two ml CCl4 added into mixture in funnel and mix well for 2 minutes (first extraction time). I2 is a mostly extracted from an aqueous phase into the organic phase. The under solution layer is the organic rose pink color phase containing 131I2. The organic phase containing 131I2 is separated. Second and third times are carried out by addition of 2,0 ml CCl4 into the extraction funnel (for second extraction time). The separation of organic phase is repeated as before. Third extraction time (1,0 ml CCl4) has be done as before. The upper aqueous phase is radioactive Tellurium solution. This solution is stored in penicilline bottle 8ml for gamma spectrometric and spectrophotometeric measurements. Extraction percentage is calculated as follows: ⎡ ⎢ nn 1 ⎢ E = 100 − 100. = 100.⎢1 − no ⎢ ⎛⎜1 + D Vdm ⎢ ⎜⎝ V H 2O ⎣
⎤ ⎥ ⎥ n ⎥ ⎞ ⎥ ⎟⎟ ⎠ ⎥⎦
with D = 85 I (CCl )/I (H O) 2 4 2 2 c. Determination of Tellurium in Na131I solution by gamma-spectrometric method: Two and half ml of bidistilled water and 100μl of Na131I solution were transferred into a separatory funnel of 60 ml volume. 100 μl solution of KI 1mg/ml as the carrier were added, 2ml of HNO3 7N were added, followed by drop by drop (∼300μl) of concentrated nitric acid into the funnel. two ml CCl4 for first extraction time. The addition of CCl4 is two ml for second extraction time and 1 ml CCl4 for third time. A 8 ml aliquot of the organic phase was taken for counting. The solution of Na131I produced at the Center for Research and Radioisotope Production was processed as Tellurium standard sample.
Fig. 1. The standard gamma spectrum of Te 10μg/ml
Fig. 2. The gamma spectrum of Te after extracted I-131 The Annual Report for 2006, VAEC
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Fig. 3. The gamma spectrum of I-131 solution
3. Determination of Tellurium in Na131I solution by spectrophotometeric methods a.Reagents: Te4+ 10mg/ml and 1mg/ml; Na2WO40,5%, H2SO46N, Polyvinylalcohol (PVA) 2%, Nile blue 0,5%. Spectrophotometer UV-VIS. b. Chemical reaction: Na2TeO3 + 12Na2WO4 + 11H2SO4 = Na4[TeW12O40] + 11Na2SO4 + 11H2O NatriñoñecacvonframoTellua C2H5 4
C2H5
N
+
O
NH2
+ [TeW 1 2 O 4 0 ] -4
H+
N B 4 [TeW 1 2 O 4 0 ]
N
N ileB lue (N B + )
c. The optimal conditions of created Te4+ - Nile Blue complex are investigated as below: D
Phoå haá p thuï cuû a phöù c vaø thuoá c thöû NB
D
0.16 0.14 0.12 0.1 0.08 0.06 0.04 0.02 0
0.15
Phöù c
D
0.15
NB
0.1
0.1
0.05 0.05
0
VH2 SO4(ml)
0
2
4
6
8
10
12
450
500
550
600
650
700
t (phuù t)
0 0
14
Fig. 4. Medium of create complex
236
400
nm 750
Fig. 5. The max bsorb of Te4+ complex and NB
The Annual Report for 2006, VAEC
30
60
90
120
150
180
210
240
Fig. 6. The durability of Te 4+ complex
VAEC-AR 06--33
D 0.2
0.25
D
Caä n döôù i vaø caä n treâ n cuû a vieä c xaù c ñònh Te 4+
Ñöôøng chuaån cuûa Te 0.2
0.2
0.15
0.05 0
0.05
CI-(mg)
0 0
0.2
0.4
0.6
0.8
1
1.2
0
0
1.4
0
Fig. 7. The impact of [ I-] on Te4+ complex
R 2 = 0.9993
0.1
0.1
0.05
y = 0.002x - 0.0081
0.15
0.15
0.1
D
20
40
60
80
100
120
140
20
40
60
80
CTe+4 100
C Te+4
160
Fig. 8. The limitation of Te 4+ concentration
Fig. 9. The curve of Te 4+ standard
The use of Te(IV) - tungstate-basic dyes - PVA systems for the determination of Tellurium has not been investigated so far. Experimentally it was found that Tellurium can react with tungstate and basic dye such as Nile blue (NB) to form ion-complexes, which was stable in the presence of PVA. This color reaction has very high sensitivity, stability and selectivity. This has been used for the determination of trace amounts of Tellurium in solution of Na131I with satisfactory results. In this annual report we have given the studied results and analytical procedure as follows: Spectral characteristics: the absorption spectra of reagent blank against water and ion-association complex of Te(IV) with tungstate in presence of PVA are recorded. The absorption maximum of the ion-association complex is at 580 nm for NB, the the absorption maximum of the reagent blank at 644 nm for NB . Effect of acidity: our experiments show the dependence of the absorbance of the ion-association complex on the solution acidity. The optimum acidity is 6N sulfuric acid for NB. Effect of reagent concentration: The optimum concentration of sodium tungstate solution is 0.5%. The optimum concentration of the basic dye (NB) is 0.5%. Effect of reaction time and stability of the absorbance: Te(IV) can react with tungstate to form a complex in 10 min at room temperature. The ion-association complex is formed in 2 min and stable at room temperature. The stability of the absorbance is as follows: at least 240 minutes for the NB system. Effect of iodine concentration: iodine concentration more than 0.8 mg/ml will affect to the absorbance. d. Determination of Tellurium in Na131I solution by spectrophotometeric method In order to determine Te content in I-131 solution (because Te content in sample is too low) we add a exact content Te into analysis sample. The determination of Te can be done by the standard scheme with Te content 20-80μg. Blank sample: 2.0ml of bidistilled water into 25.00ml flasks Standard sample: 50; 75; 100; 125; 150; 175; 200μl of standard solution Te4+ 10mg/ml into 7 flasks 25.00ml Analytical sample: 100μl I-131 solution and 100μl 10mg/ml into 25.00ml flasks
Standard solution Te4+
Add into the above flask 2.0ml of sodium Tungstate 0.5%, 6 ml sulfuric acid 6 N, 1 ml PVA 2% and NB 0.5%, and followed by water to make to 25.00ml and mix well for 10 minutes. Standard concentrations were added in flash. After shacking manually, The Annual Report for 2006, VAEC
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the mixture was allowed to stand for 10 min at room temperature. The absorbances were measured in 1 cm curvet at 580 nm against blank solution and a calibration curve was prepared. Unknown test solutions were determined directly using the graph or excel program in computer. III. Table of analytical result Tellurium content of solution of Na131I by three analytical methods Sample code
Content of Te (ppm) Spot Test
Spectrophotometeric method
Gamma spectrometeric method
200306
2-5
3,63 ± 0,15
4,85 ± 0,73
170406
2-5
4,43 ± 0,06
4,76 ± 0,66
150506
2-5
4,26 ± 0,02
4.55 ± 0,57
170706
2-5
3,35 ± 0,08
5,20 ± 0,88
140806
2-5
4,67 ± 0,32
4.90 ± 0,35
180906
2-5
3.14 ± 0,04
3.24 ± 0,45
I1140906 (Hungary)
2-5
4,44 ± 0,18
161006
1-4
3,54 ± 0,15
I5101006 (Hungary)
2-4
2,36 ± 0,17
141106
2-5
2,71 ± 0,29
I 5071106 (Hungary)
1-3
2,60 ± 0,11
3.87 ± 0,52 4.90 ± 0,67
IV. Conclution In order to control quality of Natriiodide (I-131) radiophamaceutical produced in Dalat Nuclear Research Institute, We have been studied and established three analytical processes for determining Tellurium content in Natriiodide solution. Strengths and weaknesses on methods, we viewed that the Gamma spectrum has high sensivity and exact but spend more time than other methods. So the gamma spectrometric method use for periodic control three months per once. The Spot test method is suitable than others in quality control of I-131 radiopharmaceutical in a product batch. This method can determine Te content in sample ≥ 1ppm. The process has introduced (entered) basis standard of laboratory and apply often at Center for Research and Production of Radioisotopes. The specphotometeric method only uses for reference. REFERENCES [1]. IAEA - Tecdoc - 1340, Manual for Reactor Produced Radioisotopes. IAEA January 2003, p - 86. [2]. N.Nesmeyanov. Radiochemistry. Translated from the Russian by Artavaz Beknazarov. MIR Published MOSCOW.1974.
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VAEC-AR 06--33 [3]. Ju.Lurie. Hand book of analytical Chemistry. Translated from the Russian by Nicholas Bobrov. MIR Published MOSCOW.1978. [4]. G.W.Leddicotte. The radiochemistry of Tellurium. National Academy of sciences national research Council Nuclear science series. U.S. Atomic Energy Commission. July 1961. [5]. Robert De Levie. Principes of quantitative chemmical analysis. The Mc Graw- Hill Companies, Inc, NewYork, 1997. [6]. Pharmacopia( ST) [7]. Cao Qui, Huzhide, Lizubi, Wang Jiali and Xu Qiheng. Highly sensitive spectrophotometric determination of trace amounts of Tellurium with Tungstate basic dye - poly(vinyl alcohol) system. Department of chemistry, Lanzhou University and Adult Education College, Yunnan University, China. [8]. G.Saclo.Dao Huu Vinh, Tu Vong Nghi. Methods of anlytical chemistry. Publisher of University and College HANOI - 1978. [9]. Ho Viet Qui. Methods of physical - chemistry, Publisher of education - 2000. [10]. Nguyen Ninh Trieu. Methods of physical chemistry 1Vol. Publisher of science and Technology - 2001. [11]. Hoang Nham. Organic chemistry 2 Vol. Publisher of education - 2002.
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