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Aluminium assay in biological specimens
The Science of the Total Environment, 89 (1989) 317-318 Elsevier Science P u b l i s h e r s B.V., A m s t e r d a m - - P r i n t e d in The N e t h e r l a n d s
317
A L U M I N I U M A S S A Y IN BIOLOGICAL S P E C I M E N S
S.S. K R I S H N A N
Toronto General Hospital and the Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5G 2C4 (Canada)
E X T E N D E D ABSTRACT
The quantitative assay of aluminium in brain tissue and serum is important clinically. Brain aluminium levels are associated with Alzheimer's disease (AD), and serum levels are used as an indicator of risk of bone disease in renal dialysis patients. The assay of aluminium in these specimens is difficult and is often a challenge to the analytical chemist. The considerations and difficulties in accu r ately measuring aluminium levels in these samples are discussed below. The important things to note in brain aluminium assay in AD are the sample size and sample selection criteria [1]. The sample t aken for the assay must be small in size, usually 5-10mg dry weight. Otherwise, the aluminium level assayed may be lower t han the actual level. This is because of the fact t hat the aluminium lesions in AD are localized in very small (microns size) regions, and larger samples dilute the amount by the large amount of normal tissue surrounding these lesions. Thus, the smaller the sample assayed, the higher is the probability of en c ount e r i ng these aluminium 'hot spots'. An o th er consideration is the sample selection criteria. It is important that the AD tissue contains neurofibrilliary tangles (NFTs) and t hat the normal controls used for comparison are free of them. It is the NFTs-containing tissue t h a t is high in aluminium. If this sample selection criterion is not strictly followed, there is a danger of mixing up the controls and diseased tissue, and the differences in aluminium levels between the two types may be missed. The normal serum aluminium levels are < 0.1pM1 1 (2.7pgl 1), while those of renal patients on dialysis can be as high as 12#M1 1 (323.8pgl 1). Serum or plasma aluminium level may be t aken as an indicator of aluminium toxicity. It is generally felt t hat patients with a aluminium levels > 5-7pM1-1 (134.~ 188.9pgl 1) need to be attended to in order to reduce the aluminium levels. Otherwise, these patients may be at risk of developing bone disease. Serum aluminium assay at levels mentioned above may not be easy. There are very few techniques th at are sensitive enough and simple to use routinely. Graphite furnace atomic absorption spectrometry (GFAAS) is almost exclusively used by clinical laboratories for serum aluminium assay. There are no international certified standards available at the present time for checking the accuracy of
318 t h e assay. T h e r e f o r e , in-house i n t e r n a l s t a n d a r d s a n d i n t e r l a b o r a t o r y studies a r e g e n e r a l l y used for this purpose. T h e q u a l i t y c o n t r o l for a c c u r a c y c h e c k is n o t e n t i r e l y s a t i s f a c t o r y a t the p r e s e n t time. F o r example, a c o m p a r i s o n of s e r u m a l u m i n i u m a s s a y s by 96 l a b o r a t o r i e s of a s a m p l e from the s a m e s e r u m pool showed a r a n g e of 0.84.6#M1 1 (21.6-124.1#gl 1), w i t h a m e a n of 2.2 _+ 0.5pM1 1 (59.4#gl 1). This i n t e r l a b o r a t o r y p r o g r a m w a s o r g a n i z e d by the U n i v e r s i t y of S u r r e y , U.K. It is also i m p o r t a n t to r e m e m b e r t h a t t h e r e could be u n e x p e c t e d m a t r i x interferences. T h e r e f o r e , a c c u r a c y a n d m a t r i x effects m u s t be studied t h o r o u g h l y by i n d i v i d u a l l a b o r a t o r i e s a n d the r o u t i n e a n a l y t i c a l p r o c e d u r e m u s t be established by i n t e r c o m p a r i s o n w i t h o t h e r r e p u t e d l a b o r a t o r i e s . In c o n c l u s i o n , a l u m i n i u m a s s a y in b i o l o g i c a l s a m p l e s is difficult. Careful c o n s i d e r a t i o n should be g i v e n to s a m p l e s e l e c t i o n criteria, s a m p l e size, instrumental parameters and quality control procedures. REFERENCE S.S. Krishnan, D.R. McLachlan, A.J. Dalton, B. Krishnan, S.S.A. Fenton, J.E. Harrison and T. Kruck, in Essential and Toxic Trace Elements in Human Health and Disease, Alan R. Liss, New York, 1988, pp. 645~59.
317
A L U M I N I U M A S S A Y IN BIOLOGICAL S P E C I M E N S
S.S. K R I S H N A N
Toronto General Hospital and the Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5G 2C4 (Canada)
E X T E N D E D ABSTRACT
The quantitative assay of aluminium in brain tissue and serum is important clinically. Brain aluminium levels are associated with Alzheimer's disease (AD), and serum levels are used as an indicator of risk of bone disease in renal dialysis patients. The assay of aluminium in these specimens is difficult and is often a challenge to the analytical chemist. The considerations and difficulties in accu r ately measuring aluminium levels in these samples are discussed below. The important things to note in brain aluminium assay in AD are the sample size and sample selection criteria [1]. The sample t aken for the assay must be small in size, usually 5-10mg dry weight. Otherwise, the aluminium level assayed may be lower t han the actual level. This is because of the fact t hat the aluminium lesions in AD are localized in very small (microns size) regions, and larger samples dilute the amount by the large amount of normal tissue surrounding these lesions. Thus, the smaller the sample assayed, the higher is the probability of en c ount e r i ng these aluminium 'hot spots'. An o th er consideration is the sample selection criteria. It is important that the AD tissue contains neurofibrilliary tangles (NFTs) and t hat the normal controls used for comparison are free of them. It is the NFTs-containing tissue t h a t is high in aluminium. If this sample selection criterion is not strictly followed, there is a danger of mixing up the controls and diseased tissue, and the differences in aluminium levels between the two types may be missed. The normal serum aluminium levels are < 0.1pM1 1 (2.7pgl 1), while those of renal patients on dialysis can be as high as 12#M1 1 (323.8pgl 1). Serum or plasma aluminium level may be t aken as an indicator of aluminium toxicity. It is generally felt t hat patients with a aluminium levels > 5-7pM1-1 (134.~ 188.9pgl 1) need to be attended to in order to reduce the aluminium levels. Otherwise, these patients may be at risk of developing bone disease. Serum aluminium assay at levels mentioned above may not be easy. There are very few techniques th at are sensitive enough and simple to use routinely. Graphite furnace atomic absorption spectrometry (GFAAS) is almost exclusively used by clinical laboratories for serum aluminium assay. There are no international certified standards available at the present time for checking the accuracy of
318 t h e assay. T h e r e f o r e , in-house i n t e r n a l s t a n d a r d s a n d i n t e r l a b o r a t o r y studies a r e g e n e r a l l y used for this purpose. T h e q u a l i t y c o n t r o l for a c c u r a c y c h e c k is n o t e n t i r e l y s a t i s f a c t o r y a t the p r e s e n t time. F o r example, a c o m p a r i s o n of s e r u m a l u m i n i u m a s s a y s by 96 l a b o r a t o r i e s of a s a m p l e from the s a m e s e r u m pool showed a r a n g e of 0.84.6#M1 1 (21.6-124.1#gl 1), w i t h a m e a n of 2.2 _+ 0.5pM1 1 (59.4#gl 1). This i n t e r l a b o r a t o r y p r o g r a m w a s o r g a n i z e d by the U n i v e r s i t y of S u r r e y , U.K. It is also i m p o r t a n t to r e m e m b e r t h a t t h e r e could be u n e x p e c t e d m a t r i x interferences. T h e r e f o r e , a c c u r a c y a n d m a t r i x effects m u s t be studied t h o r o u g h l y by i n d i v i d u a l l a b o r a t o r i e s a n d the r o u t i n e a n a l y t i c a l p r o c e d u r e m u s t be established by i n t e r c o m p a r i s o n w i t h o t h e r r e p u t e d l a b o r a t o r i e s . In c o n c l u s i o n , a l u m i n i u m a s s a y in b i o l o g i c a l s a m p l e s is difficult. Careful c o n s i d e r a t i o n should be g i v e n to s a m p l e s e l e c t i o n criteria, s a m p l e size, instrumental parameters and quality control procedures. REFERENCE S.S. Krishnan, D.R. McLachlan, A.J. Dalton, B. Krishnan, S.S.A. Fenton, J.E. Harrison and T. Kruck, in Essential and Toxic Trace Elements in Human Health and Disease, Alan R. Liss, New York, 1988, pp. 645~59.