Ind. Eng. Chem. Res. 2000, 39, 3151-3156
Radiation Chemistry of Simulated
99Mo
3151
Product
Susan D. Carson,* David R. Tallant, Marion J. McDonald, Manuel J. Garcia, and Regina L. Simpson Sandia National Laboratories, P.O. Box 5800, Albuquerque, New Mexico 87185
Pharmaceutical houses that produce 99mTc/99Tc generators have on occasion received product solutions of 99Mo produced from 235U fission that contained a black precipitate. Addition of sodium hypochlorite to product bottles prior to shipment prevents precipitate formation, which is evidence that the precipitate is most likely a reduced form of Mo. The radiation effects of the dose from 99Mo on the product and product bottle have been determined by irradiating simulated 99Mo product solutions with the 60Co source at Sandia National Laboratories’ Gamma Irradiation Facility (GIF). The GIF experiment successfully generated a black precipitate in amounts sufficient for isolation and analysis by infrared and Raman spectroscopy. Changes in the pH of the basic 99Mo product solution during irradiation were monitored by titration. Results of these analyses and the nature of the process that generates the precipitate, a mixture of molybdenum oxides that forms in plastic bottles but not in glass containers, are discussed. Introduction 99mTc, the decay product of 99Mo, is the most widely used radioactive isotope for diagnostic studies in nuclear medicine. 99Mo is one of the fission products produced by neutron bombardment of a 235UO2-coated stainless steel target in a reactor. After irradiation, the uranium coating is dissolved in acid and the 99Mo is isolated and purified in a hot cell facility. Because the half-life of 99Mo is only 66 h, the supply must be continuously produced and shipped to the pharmaceutical houses within 24 h of production. There is currently only one commercial producer of 99Mo in the western hemisphere, MDS Nordion of Canada. Concerned that they were limited to a single source for 99mTc, the U.S. medical community approached Congress to seek support for the development of a domestic production source of 99Mo. Congress tasked the Department of Energy (DOE) with the development of this production capability. In Sept 1996 the DOE signed a Record of Decision authorizing Sandia National Laboratories in Albuquerque to establish a production capability for 99Mo and related medical isotopes at its reactor and hot cell facilities.1 Using the existing facilities, pilot batches of 99Mo that passed industry purity specifications were produced in 1996 and shipped to pharmaceutical houses for evaluation of compatibility with their processes. Once this milestone was achieved, facilities modifications and the Food and Drug Administration validation process for full-scale production were begun. As part of process validation, possible negative effects of the high radiation field produced by 99Mo on both processing reagents and fission products were considered. β irradiation from 99Mo averages 1.12 Mrad/h and can degrade both reagents during isotope separation and the product during shipping. In the past, pharmaceutical houses have reported receiving 99Mo product solutions containing a black precipitate that forms during shipment, presumably as a result of selfirradiation.2,3 Addition of sodium hypochlorite to the product solution prior to shipment prevents precipitate
* To whom correspondence should be addressed. E-mail:
[email protected]. Fax: 505-844-1480.
formation, which is evidence that the precipitate is most likely a reduced form of 99Mo. Based on the target irradiation time, 99Mo product activity can range from approximately 2.5 Ci/mL to approximately 7.5 Ci/mL. The corresponding total dose is 17-104 Mrad for shipping times of 15-30 h. This study has used the 60Co source at Sandia’s Gamma Irradiation Facility (GIF), which produces a field intensity of approximately 1.2 Mrad/h 2 in. from the source, to determine the effects of irradiation on a simulated product solution of stable sodium molybdate under a simulated 99Mo radiation environment. Experimental Methods Simulated Product Irradiation. Four high-density polyethylene (HDPE) product bottles, each containing 80-mL aliquots (the standard product volume) of a 2% (w/v) solution of Na2MoO4‚2H2O in 0.2 N NaOH, were irradiated in the GIF. Bottles were removed after 14.4 h (sample 1-A), 28.8 h (sample 1-B), 43.2 h (sample 1-C), and 86.4 h (sample 1-D) of irradiation. These irradiation times provided a total dose to the stable molybdate samples equivalent to a self-irradiation dose from an initial product activity of 2.5 Ci/mL and 15 h shipping time (sample 1-A), 2.5 Ci/mL and 30 h shipping time (sample 1-B), 7.5 Ci/mL and 15 h shipping time (sample 1-C), and 7.5 Ci/mL and 30 h shipping time (sample 1-D), respectively. The 2% molybdate solution was approximately 54 times more concentrated than an average product solution to ensure that, if formed, enough precipitate would be available for isolation and identification. However, because a black precipitate readily formed in these solutions after 14.4 h, it was decided to irradiate three additional sets of samples: 1. Two 80-mL samples, labeled 1-DIL and 2-DIL, each containing 0.145 mmol of Na2MoO4‚2H2O in 0.2 N NaOH. These samples simulated a typical production scenario and contained the maximum amount of molybdenum (product and carrier) that would be present after a 6-h cooldown from a 20-g target irradiated for 7 days at 15 kW. It was decided that 1-DIL would be pulled at whatever of the remaining sampling times a
10.1021/ie990378+ CCC: $19.00 © 2000 American Chemical Society Published on Web 07/11/2000
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Ind. Eng. Chem. Res., Vol. 39, No. 9, 2000
precipitate was first detected and that 2-DIL would be irradiated for the full 72 h remaining in the test series. 2. Two 25-mL samples, labeled 1-G and 2-G, of the 2% molybdate solution in clear, colorless glass bottles. Because of the pattern of black precipitates seen on the 1-A-1-D HDPE bottles after 14.4 h, precipitate appeared to be forming on the bottle surface, building up, and then sloughing off to the bottom of the bottle. Bottle surfaces were darkest in the area closest to the 60Co source. On the basis of these observations, it was decided to determine if the precipitate would form in a glass container. Samples were smaller, because of the size of the glass bottles that were available. These samples were pulled using the same sample protocol as that of 1-DIL and 2-DIL; i.e., 1-G was removed when precipitate was first observed and 2-G was left in the GIF for 72 h. 3. Two 50-mL samples, labeled 1-OH and 2-OH, of 0.2 N NaOH in the HDPE product bottles. These were run to compare any decrease in the base strength that might occur in the molybdate solution with the behavior of a sodium hydroxide blank under the same conditions. Because there was not enough room in the sample container, these two samples were not put in the GIF until the 28.8-h samples were removed, so they were only irradiated a total of 57.6 h. Samples of a 2% basic molybdate solution containing NaOCl were also irradiated and removed at the time intervals of 14.4, 28.8, 43.2, and 86.4 h. Because producers of 99Mo normally add 2 mg of hypochlorite/ Ci of 99Mo activity, four bottles (samples 2-A-2-D) contained 3.5 mL of 10-13% (w/v) aqueous NaOCl (the amount required for 2.5 Ci/mL, 80 mL of product) and four (samples 3-A-3-D) contained 10.5 mL (the amount required for 7.5 Ci/mL, 80 mL of product). Sample descriptions and irradiation times are summarized in Table 1. Titration Data. After removal from the GIF, 20-mL aliquots of samples containing precipitate (1-A-1-D, 1-DIL, and 2-DIL) were set aside and allowed to stand at room temperature. Remaining sample volumes were filtered through Fisher P8 fluted filter paper to remove any precipitate. Duplicate aliquots of the filtered samples were titrated to a phenolphthalein end point with standardized 0.1974 N HCl that had been standardized with 0.3938 N NaOH. The latter was standardized to a phenolphthalein end point with potasssium hydrogen phthalate. Because of their smaller initial volume, single samples of 1-G, 2-G, 1-OH, and 2-OH were titrated. Because each G and OH sample experienced the same total irradiation time, this was equivalent to duplicate samples. Unirradiated samples of the 2% molybdate solution were also titrated prior to irradiation and after standing at room temperature for 86.4 h. Infrared and Raman Spectra. Any precipitate that formed was washed to a neutral pH, air-dried, and analyzed using Fourier transform infrared (FTIR) and Raman spectroscopy. FTIR transmission spectra were obtained using a Nicolet model 800 SX spectrometer with a SpectraTech microscope attachment (resolution 8 cm-1). Raman spectra were obtained using 514-nm excitation, a triple spectrograph with a charge-coupleddevice (CCD) detector, and a microscope accessory (∼1µm spatial resolution). Results Visual Inspection. Samples 1-A-1-D contained black precipitate after 14.4 h of irradiation. The pre-
Table 1. Sample Summary sample vol, ID mL 1-A
80
1-B
80
1-C
80
1-D
80
2-A
80
2-B
80
2-C
80
2-D
80
3-A
80
3-B
80
3-C
80
3-D
80
1-DIL
80
2-DIL
80
1-G
25
2-G
25
1-OH 2-OH
50 50
sample description 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, 3.5 mL of 10-13% (w/v) aqueous NAOCl, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, 3.5 mL of 10-13% (w/v) aqueous NAOCl, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, 3.5 mL of 10-13% (w/v) aqueous NAOCl, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, 3.5 mL of 10-13% (w/v) aqueous NAOCl, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, 10.5 mL of 10-13% (w/v) aqueous NAOCl, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, 10.5 mL of 10-13% (w/v) aqueous NAOCl, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, 10.5 mL of 10-13% (w/v) aqueous NAOCl, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, 10.5 mL of 10-13% (w/v) aqueous NAOCl, HDPE bottle 0.145 mmol of Na2MoO4‚2H2O in 0.2 N NaOH, HDPE bottle 0.145 mmol of Na2MoO4‚2H2O in 0.2 N NaOH, HDPE bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, clear, colorless glass bottle 2% (w/v) Na2MoO4‚2H2O in 0.2 N NaOH, clear, colorless glass bottle 0.2 N NaOH, HDPE bottle 0.2 N NaOH, HDPE bottle
irradiation time, h 14.4 28.8 43.2 86.4 14.4 28.8 43.2 86.4 14.4 28.8 43.2 86.4 28.8 72 72 72 57.6 57.6
cipitate appeared to initially form on the walls of the sample bottles, and the amount of precipitate steadily increased with irradiation time. Black precipitate was first noticed in samples 1-DIL and 2-DIL after 28.8 h of irradiation. No visible changes were observed in sample solutions 2-A-2-D, 3-A-3-D, 1-G, 2-G, 1-OH, or 2-OH. Gas was released when caps on samples 2-A2-D and 3-A-3-D were loosened. HDPE bottles turned yellow and the glass bottles turned dark brown, both normal and expected consequences of extended exposure to γ irradiation. Precipitate in the 20-mL aliquots that were allowed to stand at room temperature slowly returned to solution. Solutions were clear and colorless. Dissolution times ranged from 24 h (samples 1-A and 1-DIL) to 4 weeks (sample 1-D). Titration Data. Titration results are summarized in Tables 2 and 3. Data in Table 2 are the average of duplicate aliquots of each sample. Titration of a blank consisting of 2% Na2MoO4‚2H2O in water required less than 1 drop of HCl. The unirradiated 2% molybdate sample that was titrated at the conclusion of the 86.4 h of GIF time had a normality of 0.194, in good agreement with initial values. Once the black precipitate had dissolved, the 20-mL aliquots were titrated, as were samples of residual 1-OH and 2-OH, which were used as controls (Table 3). No data are shown for the 20-mL aliquot of 1-A because it was inadvertently discarded.
Ind. Eng. Chem. Res., Vol. 39, No. 9, 2000 3153 Table 2. Initial Titration Data sample
mequiv of base/ mL of samplea
unirrad, t ) 0 s 1-A 1-B 1-C 1-D 1-DIL 2-DIL G OH unirrad, t ) 86.4 s
0.198 0.186 0.185 0.193 0.198 0.194 0.186 0.185 0.186 0.194
a
∆, mequiv/mL -0.012 -0.013 -0.004 -0.004 -0.012 -0.013 -0.012 -0.004
Average standard deviation ) (0.004.
Table 3. Titration of 20-mL Aliquots with Dissolved Precipitate
a
sample
mequiv of base/ mL of samplea
∆, mequiv/mL
1-B 1-C 1-D 1-DIL 2-DIL OH
0.183 0.181 0.187 0.188 0.181 0.192
-0.015 -0.017 -0.011 -0.010 -0.017 -0.006
Average standard deviation ) (0.004.
Data in Table 2 show a pattern of an initial decrease in sample basicity, followed by an increase at longer irradiation times in samples 1-C and 1-D. A comparable decrease is also seen in 1-OH and 2-OH after 72 h of irradiation. Once the precipitate dissolves, sample basicity in Table 3 again decreases relative to the residual 1-OH and 2-OH samples, whose basicity appears to have increased slightly with standing. While these trends appear to exist, it should be noted that they are at the limit of detection (the largest decrease in Table 2, 0.013, is only 3.25 times the standard deviation) by this titration method. Infrared Data. Figure 1 presents infrared data for unirradiated Na2MoO4‚2H2O, the FTIR library spectrum of Na2MoO4‚2H2O, and the spectrum of precipitate from sample 1-D. Bands corresponding to the stretching frequencies for the Mo-O bond in Na2MoO4‚2H2O were observed at 907, 874, 838, and 805 cm-1 in samples of pure neat compound. These bands were identical in frequency to the Na2MoO4‚2H2O spectrum in the spectrometer’s computer library and agreed well with literature values (903, 898, 855, 820, and 805 cm-1).4 As the irradiation time increased, the bands narrowed into a single band whose peak tended to shift to lower frequency. Sample 1-D contained a single strong, sharp Mo-O band at 833 cm-1. The fact that this peak is present indicates oxide(s) other than MoO2 are likely present, because the latter is a symmetric molecule and IR-inactive. Although precipitates were washed several times and dried prior to IR analysis, all sample spectra contained a peak at 1434 cm-1 because of the presence of NaOH crystals. While the broad peak above 3000 cm-1 may contain absorptions due to metal hydroxide(s), OH, and/ or waters of hydration, this cannot be ascertained, because of the presence of NaOH. Raman Data. A Raman spectrum of unirradiated Na2MoO4‚2H2O had a strong, sharp Mo-O stretching frequency at 894 cm-1 and a medium intensity band at 842 cm-1 with an unresolved low-frequency shoulder, in excellent agreement with literature values of 897, 843, 836, and 805 cm-1.5 Raman spectra for the black
precipitate from samples 1-C, 1-D, 1-DIL, and 2-DIL are shown in Figure 2. At low laser excitation power (0.5 mW at the microscope entrance and about 10 times lower at the sample), the filtered residues are stable and yield broad Raman bands characteristic of amorphous (glassy) materials. Similar spectra (but with the bands near 870 and 950 cm-1 more clearly separated) were obtained by Haro-Poniatowski et al. for amorphous hydrated MoO3.6 When their samples were exposed to higher laser power, Haro-Poniatowski et al. observed the formation of the R and β crystalline forms of MoO3. In an analogous experiment, two areas of sample 1-D and one area of sample 1-C were exposed to 10 mW of laser power in order to crystallize the amorphous material by laser annealing. Results are shown in Figure 3. The narrow Raman bands resulting from laser annealing fall within the envelope of bands defined by MoO3 (Mo-O stretching frequencies at 997 and 820 cm-1 for R-MoO3 and 904, 849, and 773 cm-1 for β-MoO37) and Na2MoO4‚ 2H2O. The spectrum of laser-annealed sample 1-D also contains peaks (730, 490, 360, and 200 cm-1) that match the strongest Raman peaks for MoO2 (744, 495, 363, and 203 cm-1).8 Similar complex Raman spectra were obtained by Spevack and McIntyre in their study of the thermal reduction of MoO3.8 The differences in the Raman spectra of annealed 1-C and 1-D are most likely due to varying composition in the areas irradiated and localized annealing conditions. On the basis of the preceding spectral data and the fact that precipitate only forms in samples in HDPE bottles, it is concluded that the black precipitate is most likely composed of a complex mixture of reduced molybdenum oxides, MoOx, 2 < x
