Fresenius J Anal Chem (1995) 352:219-223 Fresenius' Journal of

@ Springer-Verlag t995

Application of synthetic reference materials in the Medical Radiological Research Centre

V. Ye. Zaichick

Medical Radiological Research Centre, Obninsk 249020, Kaluga Region, Russia

Received: 25 July 1994 / Revised: 20 February 1995 / Accepted: 26 February 1995

Abstract . The contents of 21 chemical elements (Ag, Br, Ca, C1, Co, Cr, Cs, Fe, Hg, K, Mg, Mn, Na, R Rb, Sb, Sc, Se, Sr, Zn, Zr) in synthetic reference materials (SRMs) were compared with those in natural reference materials (NRMs) using short- and long-lived radionuclides. SRMs called synthetic standards (SSs) and synthetic standards, biolog- ical (SSBs) were prepared on the basis of phenol-formalde- hyde resol resins in the Institute of Physics, Georgian Academy of Science. The NRMs included such IAEA ref- erence materials as H-4 (animal muscle), A-13 (animal blood), H-5 (animal bone), SL-1 (lake sediment), SOIL-7 (soil), A-9 (mixed human diet), and IAEA-153 (milk powder). It was shown that SSB-SRMs possessed good representativity of the 30-50 mg tablets, high precision, operational convenience, and could be recommended for the INAA of a wide range of medico-biological and bio- ecological objects.

Introduct ion

Instrumental neutron activation analysis (INAA) is one of the most promising methods for studying the element con- tents in the human body. However, the effective applica- tion of INAA in clinical, toxicological, and environmental medicine is partly limited by the shortcomings of metro- logical provisions and, in particular, the lack of a suffi- ciently broad set of reference materials (RMs). There are two ways to create RMs. One is the application of natural materials (NRMs). The other is to create synthetic refer- ence materials (SRMs) based on a synthesis with element concentrations close to those found in NRMs.

In spite of certain difficulties of SRM preparation by perfect technologies, SRMs possess a number of advan- tages:

- element concentrations are known a priori; - the broadest set of SRMs can be unlimited and pro-

vided quickly; - matrix substances with more technological properties

than the natural object studied can be used.

Since 1974 SRMs have been used for the INAA of medical and biological objects by the Medical Radiologi- cal Research Centre (MRRC). The studies were generally related to solving problems of clinical medicine until the early '80s. Different human tissues and fluids were ana- lyzed both for the standard and for various diseases (mainly oncological). Studies of extreme conditions of long-term space flights were also carried out. Since the mid '80s INAA has been used to solve medical problems related to environmental hazards and conditions in a number of Russian regions. The Chernobyl disaster contributed to the expansion of such studies. Element contents were an- alyzed in a very broad set of materials including: soil, lake sediment, river sediment, dry-land plants, water plants, mosses, lichens, fish tissue, wild animal tissue, food prod- ucts, mixed human diet, mother's-milk, and others.

In these studies we used a universal set of SRMs which was modified according to the results of checking parameters. The preparation of the IAEA NRMs in the early '80s greatly favoured the development of these studies.

The purpose of the study described in this paper was to estimate the SRM precision using them along with NRMs during INAA.

Materials and methods

Materials. Between 1974 and 1984 we used SRMs called synthetic standards (SS) prepared on the basis of phenol- formaldehyde resol resins in the Institute of Physics, Georgian Academy of Sciences, specifically for INAA [1]. The SSs were 6 mm diameter tablets weighing 30-50 mg. Their element contents are given in Table 1.

Since 1985 we used SSBs (synthetic standards, biolog- ical) as SRMs. Their compositions are shown in Table 2.

In 1980 SSs were used for the INAA of IAEA refer- ence material H-4 (animal muscle) to estimate the preci- sion of its certified values. The same SRMs were used to analyze such IAEA reference materials as A-13 (animal blood) and H-5 (animal bone) when the MRRC partici-

2 2 0

Tab le 1. Composit ion of SRMs called synthetic standards (SS) prepared on the basis of phenol-formaldehyde resins in the Insti- tute of Physics, Georgian Academy of Sciences, 1974 [1]

Table 2. Composition of SRMs called synthetic standards, biological (SSB) prepared on the basis of phenol-formaldehyde resins in the In- stitute of Physics, Georgian Academy of Sciences, in the mid '80s

Element Element concentration, btg/g

SS-0 SS-1 SS-2 SS-3

Element Element concentration, btg/g

SSB-1 SSB-2 SSB-3

Ag 3.02 2.98 - -

Au 0.0101 - 0.0100 -

Ba 504 - 502 -

Br 20.2 - 20.2 -

Co 3.02 2.98 - -

Cr 10.1 9.93 - -

Cs 1.01 - 1.00 -

Fe 301 297 - -

Hg 10.1 9.93 - -

K - - 1000 -

La 0.301 - - 0.308

Na 3020 - 3010 -

Nd 1.01 - - 1.03

Ni 10.1 - 10.0 -

Rb 30.2 29.8 - -

Sb 0.302 0.298 - -

Sc 0.101 - 0.100 -

Se 5.04 4.97 - -

Sn 50.4 - 50.2 -

Tb 0.504 - - 0.515

Zn 101 99.3 - -

Zr 0.508 - - 0.519

p a r e d in t he i n t e r - l a b o r a t o r y s t u d y o f t he a g e n c y ' s m a t e r -

ia l in 1 9 8 1 - 8 2 . S S B s w e r e u s e d f o r t he I N A A o f s u c h I A E A r e f e r e n c e

m a t e r i a l s as S L - 1 ( l ake s e d i m e n t ) , S O I L - 7 (soi l ) , A - 9 ( m i x e d h u m a n d ie t ) , a n d I A E A - 1 5 3 ( m i l k p o w d e r ) to as-

sess t he p r e c i s i o n o f t h e i r c e r t i f i e d va l ue s .

Samples. F o r the I N A A w i t h s h o r t - l i v e d r a d i o n u c l i d e s , the

SS a n d S S B tab le t s a n d I A E A sample s , e a c h w e i g h i n g 3 0 - 50 mg , w e r e sea led in a t h in p o l y e t h y l e n e f i lm, w a s h e d w i t h a c e t o n e a n d r e c t i f i e d a l coho l . T h e s e a l e d t a b l e t s a n d s a m - p l e s w e r e t h e n p l a c e d in l a b e l l e d p o l y e t h y l e n e a m p u l e s .

F o r t he I N A A w i t h l o n g - l i v e d r a d i o n u c l i d e s , t he SS

a n d S S B t a b l e t s a n d I A E A s a m p l e s w e r e w r a p p e d sepa - r a t e l y in h i g h - p u r i t y a l u m i n i u m foil .

Irradiation. T h e h o r i z o n t a l c h a n n e l o f t he V V R - C n u c l e a r r e a c t o r w a s u s e d to a n a l y z e Br, Ca , C1, K, M g , M n , Na , S r fo r t he I N A A w i t h s h o r t - l i v e d r a d i o n u c l i d e s . T h e c h a n n e l w a s e q u i p p e d w i t h p n e u m a t i c s a n d c o o l e d w i t h c o m - p r e s s e d air. T h e n e u t r o n f lux d e n s i t y in t he c h a n n e l w a s 1.7 x 1013 n cm-2s -1. A m p u l e s w i t h I A E A s a m p l e s a n d SS

o r S S B t a b l e t s w e r e g i v e n i n to p o l y e t h y l e n e t r a n s p o r t c o n t a i n e r s a n d t h e n i r r a d i a t e d s e p a r a t e l y f o r 2 0 - 2 0 0 s. C o p p e r fo i l s w e r e u s e d to p r e c i s e l y d e t e r m i n e the n e u t r o n f lux . T h e y w e r e p l a c e d in t he t r a n s p o r t c o n t a i n e r a n d i r ra- d i a t e d s i m u l t a n e o u s l y w i t h t h e t a b l e t s a n d I A E A s a m p l e s .

Ag 1.72 - 0.0085

A1 - - 0.34

As - - 0.0017

Au 0.026 - 0.0085

Ba - 10.6 0.04

Br - 20.7 4.22

Ca - 3740 51

Cd - - 0.0043

C1 - - 2900

Co 0.63 - 0.0084

Cr 1.78 - -

Cs - 0.48 0.0042

Cu - - 0.85

Fe 296 - 425

Hg - 0.096 0.017

K - - 1360

Mn - 0.042

Na - 3660 1702

Ni - 9.54 0.085

Rb 9.05 - -

Sb 0.45 - 0.0017

Sc - 0.037 0.0059

Se 2.84 - 0.17

Sn - 24 0.068

Sr - - 0.026

Zn 19.5 - 4.25

F o r the I N A A w i t h l o n g - l i v e d r a d i o n u c l i d e s the ve r t i -

ca l r e a c t o r c h a n n e l w a s u s e d to a n a l y z e Ag , Co, Cr, Cs , Fe , Hg , Rb , Sb , Sc, Se , Z n a n d Zr. It h a d a n e u t r o n f lux d e n s i t y o f 1.2 × 1013 n cm-2s -1. T h e t a b l e t s a n d I A E A

s a m p l e s w e r e w r a p p e d in a l u m i n i u m fo i l a n d g i v e n i n to q u a r t z a m p u l e s w a s h e d w i t h n i t r i c ac id . T h e q u a r t z a m - p u l e s w e r e sea led , p l a c e d in a n a l u m i n i u m t r a n s p o r t c o n -

t a i n e r a n d i r r a d i a t e d fo r 2 4 - 1 2 0 h.

Spectrometry. M e a s u r e m e n t s w e r e m a d e t w i c e fo r t he I N A A w i t h s h o r t - l i v e d r ad ionuc l i de s : 1 -5 m i n and 1 .5 -3 h a f t e r i r r a d i a t i o n . T h e d u r a t i o n o f t he f i r s t m e a s u r e m e n t w a s 5 - 1 0 m i n , t he s e c o n d m e a s u r e m e n t l a s t e d 2 0 - 3 0 m i n . M e a s u r e m e n t s w e r e s t a r t ed 1 5 - 9 0 d a y s a f t e r i r r a d i a t i o n fo r t he I N A A w i t h t he l o n g - l i v e d r a d i o n u c l i d e s . T h e du ra - t i o n o f t h e s e m e a s u r e m e n t s w e r e 1 - 2 0 h.

I N A A c o n d i t i o n s ( t i m e o f i r r a d i a t i o n , d e c a y a n d m e a - s u r e m e n t , s a m p l e - d e t e c t o r d i s t ance ) we re o p t i m i z e d for the m a x i m u m n u m b e r o f c h e m i c a l e l e m e n t s w i t h a m i n i m u m s t a t i s t i ca l e r r o r o f m e a s u r e m e n t . T h e s e c o n d i t i o n s w e r e c a l c u l a t e d in a d v a n c e fo r e a c h s p e c i f i c m a t e r i a l u s i n g a s p e c i a l l y d e v e l o p e d c o m p u t e r p r o g r a m [2, 3].

Table 3. INAA data a of major and trace elements of IAEA reference material compared with certified values (gg/g dry mass)

221

Ele- Animal muscle H-4 Animal blood A-13 Animal bone H-5 ment

Own results [4] Certified values [5] Own results Certified values [6] Own results Certified values [7] Mean _+ S.E. 95% Confidence Mean _+ S.E. 95% Confidence Mean _+ S.E. 95% Confidence

interval interval interval

Ag 0.033 _+ 0.008 0.0023 _+ 0.0005 - 0.030 + 0.011 -

Br 5.0 + 0.7 3.5-4.7 19.8 + 0.9 19-24 - 3.27-3.98

Ca - 163-213 - 226-332 210800 + 3200 202980-220430 C1 - 1810-1970 12980 + 220 (10600-17600) 968 _+ 220 423-682

Co 0.0074 _+ 0.0018 (0.0020-0.0035) 0.018 + 0.006 (0.0051-2.51) 0.22 _+ 0.08 0.16-0.33

Cr 0.071 + 0.010 (0.030-0.080) 0.193 + 0.031 (0.061-1.90) 1.44 _+ 0.40 1.80-3.31

Cs - 0.11-0.14 0.0077 _+ 0.0008 - - -

Fe 47 _+ 1 47-51 2430 _+ 240 2200-2500 94 +_ 9 76.6-84.8

Hg 0.62 _+ 0.09 0.010-0.017 < 0.015 (0.0038-0.0746) - 0.0012-0.0149

K 16200 _+ 3800 15300-16400 - 2100-2800 - 563-706

Mg - 990-1110 - (81.4-139.2) 3500 _+ 400 3430-3640

Mn - 0.48-0.55 0.78 _+ 0.04 (0.0008-0.065) - 0.63-0.89

Na 2190 _+ 140 1930-2180 12100 _+ 200 11600-13500 3070 _+ 160 4400-5130

pb _ (2010--11640) - (687-Ii16) 138800 _+ 4600 73740--117810 Rb 23.7 _+ 1.0 17-20 2.36 _+ 0.26 1.7-3.1 < 1.5 0.25-1.90

Sb - (0.0032-0.0080) 0.0124 _+ 0.0021 (0.020-21.2) 0.023 _+ 0.006 0.0127-0.0362 Sc 0.0025 _+ 0.0007 (0.0025-0.0036) 0.0051 + 0.0015 (0.0028) < 0.001 -

Se 0.281 _+ 0.014 0.250-0.320 0.25 _+ 0.07 0.150-0.305 0.051 _+ 0.009 0.0335-0.0740

Tb . . . . < 0.007

Zn 91 _+ 2 83-90 12.7 _+ 1.6 12-14 83.4 _+ 1.8 85.2-94.6

a Data were obtained using SRM prepared in 1974 [1] b p was analyzed by INAA using the 14 MeV neutrons [8] ( ) Non-certified values

The 40 cm 3 Ge(Li) detector and mul t i -channel ana- lyzer (MCA) were used for spectrometry in the '70s. Be- g inn ing in the mid '80s the 100 cm 3 Ge(Li) detector and on-l ine computer-based M C A system were used.

Results and discussion

Reproducib i l i ty of the methods and representat ivi ty of the SS tablets and the 30 mg IAEA H - 4 samples were checked by irradiating 5 tablets of one and the same num- ber, and 5 I A E A samples [4]. It was shown that for the I N A A of the SS tablets the variat ion coefficient for the re- sults of est imation was:

Ag 4% Fe 12% Rb 18% Br 8% Hg 54% Sb 15% Co 5% K 17% Sc 3% Cr 18% Na 5% Se 10%

Tb 8% Zn 8%

Values for such elements as Cr, Hg, K, Rb, Se were higher than those for the 30 mg H - 4 samples. Moreover, slightly increased values for Br, Rb, Zn, when compared with the certified values, were found fol lowing the est imation of absolute e lement concentrat ions in H - 4 using the SSs (Table 3). The result for Hg was totally inadequate. Its concentrat ion was about 50 times higher than the certified

value. These results showed that an insufficient homo- geneity in the distr ibution of several elements as Br, Rb, and Zn could be lost in the process of SRM preparation. It was also shown that the SSs were totally useless for the analysis of Hg, due to a considerable loss of the e lement (up to 98%) and an extremely non-homogeneous distribu- t ion [4].

Nevertheless, we used SS tablets in our studies after in t roducing some proper correction factors including the determinat ion of major and trace elements in such new IAEA reference materials as A - 1 3 (animal blood) and H - 5 (animal bone). Studies on the certification of these reference materials for trace e lement analysis were orga- nized by I A E A in the early '80s. Our results are given in Table 3. Compar ison with a summary of the comparison data showed that the mean concentrat ion of each element studied was within the 95% confidence interval.

In the mid '80s the Georgian scientists took account of their own SRM experience and our remarks [4] and pro- duced a new modif ied set of SSBs. This biological SRM set was specially prepared for I N A A of biological objects. We compared the SS I N A A and the SSB INAA. It was shown that the SSB tablets were more representative than the SS tablets for almost every element (of equal weight).

We used SSBs for the I N A A of major and trace ele- ments in such new IAEA reference materials as H - 9

2 2 2

Tab le 4. I N A A data of major and trace elements of IAEA reference material prepared f rom food products and compared with certified values (gg/g dry mass)

Element Mixed human diet H - 9 Milk powder I A E A - 1 5 3

O w n results Certified values [9] O w n results Certified values Mean _+ S.E. Mean _+ S.E

Mean 95% Confidence Mean 95% Confidence interval interval

Ag 0.018 + 0.003 - - < 0.01 - -

Br < 9.0 7.5 6.8-8.2 11.6 + 1.7 12.3 11.0-13.6

Ca 2800 _+ 350 2310 2150-2470 12640 _+ 680 12900 12500-13200

C1 12300 + 300 12500 11000-14000 7280 + 40 - -

Co 0.046 + 0.002 0.043 0.038-0.048 0.027 + 0.004 - -

Cr 0.164 _+ 0.016 0.15 0.11-0.19 <0.07 - -

Cs 0.029 + 0.002 0.025 - 0.0118 + 0.0007 - -

Fe 35.7 + 3.9 33.5 31-36 3.4 + 0.6 2.53 1.66-3.47

Hg < 0.01 0.0048 0.0034-0.0062 < 0.02 - -

K 8100 + 500 8300 7600-9000 17640 + 340 17600 16480-18760

Mg 760 + 200 785 730-840 1230 + 80 1060 1000-1150

Mn 11.2 + 1.3 11.8 11.0-12.6 0.60 _+ 0.09 - -

Na 8400 _+ 200 8100 7400-8800 4170 + 60 4180 3870-4440

Rb 8.6 _+ 0.2 8.0 7 .4-8.6 18.8 + 1.5 14.0 12.3-16.1

Sb 0.016 _+ 0.002 - - 0.0009 _+ 0.0003 - -

Sc 0.0022 _+ 0.0003 - - 0.0038 _+ 0.0009 - -

Se 0.12 _+ 0.02 0.11 0.10-0.12 < 0.05 - -

Sr < 30 3.0 2.6-3.4 < 50 - -

Tb - - - < 0.002 - -

Zn 28.8 + 1.0 27.5 25.7-29.3 46.9 + 0.4 39.6 37.7-41.2

Tab le 5. I N A A data of major and trace elements of I A E A reference material prepared f rom lake sediment and soil, and compared with certified values (gg/g dry mass)

Element Lake sediment SL-1 S O I L - 7

O w n results Certified values O w n results Certified values Mean + S.E. Mean + S.E

Mean 95% Confidence Mean interval

95% Confidence interval

Ba 648 + 41 639 586-692 183 + 41 (159)

Ca - - - 164000 _+ 11000 (163000)

Co 18.9 _+ 0.8 19.8 18.3-21.3 9.1 +_ 0.4 8.9

Cr 101 + 4 104 95-113 60.5 _+ 3.5 60

Cs 6.52 + 0.65 7.01 6.13-7.89 5.5 _+ 1.0 5.4

Fe 62400 _+ 3500 67400 65700-69100 23700 + 950 (25700)

K 15800 + 2000 (15000) - 10950 +_ 1500 (12100)

Mg 22800 _+ 5100 (29000) - 11400 _+ 1600 (11300)

Mn 3250 + 150 3400 3240-3560 603 _+ 21 631

Na 1680 + 80 1720 1600-1840 2210 + 90 (2400)

Rb 121 _+ 3 113 102-124 57.2 + 8.7 51

Sb 1.37 + 0.16 1.31 1.19-1.43 1.77 + 0.22 1.7

Sc 9.84 _+ 0.08 a 17.3 16.2-18.4 5.38 _ 0.07 b 8.3

Zn 228 + 15 223 213-233 97 + 9 104

Zr 220 + 30 (241) - 198 _+ 21 185

(131-196)

(157000-174000)

8.4-10.1

49-74

4.9-6.4

(25200-26300)

(11300-12700)

(11000-11800)

604-650

(2300-2500)

47-56

1.4-1.8

6.9-9.0

101-113

180-201

a This value is 1.7 t imes lower than the certified mean value and is not within the 95% b This value is 1.5 t imes lower than the certified mean value and is not within the 95% ( ) Non-cert if ied values

confidence interval confidence interval

223

(mixed human diet), IAEA-153 (milk powder), SL-1 (lake sediment), and SOIL-7 (soil). The results are given in Table 4 and 5. Comparison of the INAA data with the certified values for the IAEA reference materials con- firmed the high SSB precision. Our data for the mean val- ues of the elements Ba, Br, Ca, C1, Co, Cr, Cs, Fe, K, Mg, Mn, Na, Rb, Sb, Se, Zn, and Zr were always within the 95% confidence interval. The only exception was Sc, the values of which were 1.5-1.7 times lower than the certi- fied values. Unfortunately, we could not check SSB preci- sion of Hg because of its high detection limit, due to the imperfection of the spectrometric equipment used.

The tablet-shaped 30-50 mg SRMs prepared on the basis of phenol-formaldehyde resins have many advantages in addition to their high representativity and the precision of their element concentrations. High radiation resistance is one major advantage. During irradiation of biological materials with neutron fluxes of about 1019-102o n cm -2, weight losses can be up to 30 -40% following radiolysis. In spite of the registration of the weight change, such losses of the organic matrix adversely affect data preci- sion. The main components of phenol-formaldehyde resins are hydrogen, carbon, and oxygen. A biological matrix has the same components. However, the SSB tablets loose not more than 5% of their weight and keep their shape, even with a neutron flux of 102o n cm -2. The lower the loss of the main matrix, the lower the possible loss of the trace elements analyzed. When the shape is kept intact, more precise spectrometry is possible. Furthermore, the tabletshaped SRMs with smooth, solid surfaces are rather

convenient for weighing, wrapping before irradiation, and re-wrapping after irradiation.

The data of our study make it possible to conclude that SRMs based on solid solutions of chemical elements, con- tained in phenol-formaldehyde resol resins, possess con- siderable advantages for INAA applications. These ad- vantages are: good representativity of the 30-50 mg tablets, high precision, and operational convenience. SSBs can be recommended for the INAA of a wide range of medico-biological and bio-ecological objects.

References

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2. Zaichick V (1978) Med Radiol 9:47-50 3. Korelo A, Zaichick V (1994) Neutron activation analysis in en-

vironment. JINT, Dubna 4. Zaichick V, Kalashnikov V (1985) Nuclear methods for envi-

ronmental monitoring. Gidrometeoizdat, Leningrad 5. Parr (1980) Inter-comparison of minor and trace elements in

IAEA animal muscle (H-4). Report No 2, IAEA, Vienna 6. Pszonicki L, Hanna A, Suschny O (1983) Report of intercom-

parison A-13 of the determination of trace elements in freeze dried animal blood. IAEA/RL/98, Vienna

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