Iranian Journal of Pharmacology and Therapeutics Razi Institute for Drug Research (RIDR) of Iran University of Medical Sciences and Health Services (IUMS) ISSN: 1735-2657 Vol. 4, Num. 1, 2005, pp. 40-42

Iranian Journal of Pharmacology & Therapeutics, Vol. 4, No. 1, 2005, pp. 40-42

Evaluation of Aluminum Concentration in Albumin Products Prepared by Blood Fractionation

TAHEREH ZANDIEH and SODABEH BANAZADEH

Research Center of Iranian Blood Transfusion Company, Tehran, Iran.

Address correspondence to: Dr. Tahereh Zandieh, Manager Department, Iranian Blood Transfusion Organization, P.O.Box: 11/1745, Tehran, Iran. E-mail: tz7892000@yahoo.com

Received May 28, 2005;
Revised June 8, 2005;
Accepted June 11, 2005

Code Number: pt05010

ABSTRACT

Human Serum albumin as well as other biological products prepared by blood fractionation for clinical purposes, was found to contain different amount of aluminum in different commercially available human albumin solutions. It has been reported that interaction of chemicals with the container material can occur during plasma collection, manufacture and storage, so aluminum is introduced into albumin products. Al-bumin solution is produced by Cohn fractionation. These solutions were analyzed and albumin content was measured by atomic absorption spectrometry, using electrothermal atomizer (Graphite Furnace) and the aluminum concentration in final products and in-process fractions in 21 batch of albumin 20% and 8 batch of albumin 5% were investigated. Also the content of aluminum was determined after 3 months storage in glass container. We found that the aluminum content in all investigated containers had re-markably reduced during the fractionation process. Only in one stage the aluminum content has been increased, and it is probably due to the filters and other chemicals which are used to adjust pH and elec-trolyte concentration. On the other hand concentration may have an important role in increasing alumi-num content in this stage. Aluminum overload may result in development of some diseases, so indicating the need to monitor aluminum level in the albumin to avoid the potential hazard.

Keywords: Aluminum, Albumin, Atomic absorption, Plasma fractionation

Human serum albumin is the most plentiful plasma protein, and considered as the most physiological solu-tion for volume loading, can be widely used in patients with renal, cardiac and respiratory injuries. Human Se-rum albumin products are used to treat hypoalbuminae-mia or hemorrhagic shock. The contamination of albu-min by metals especially by aluminum, is a major con-cept in preparing albumin solutions, because aluminum toxicity in human being has been increased in patients receiving hemodialysis, and patients who had died with dialysis encephalopathy syndrome had brain gray matter aluminum levels that were 3 times higher the normal [ 1 ].

Aluminum is introduced into albumin products via materials (Diatomaceous earth filters aid or diatoma-ceous containing depth filters) used in manufacturing process, resulting in a high aluminum level in the final product [ 2 ]. Sodium citrate, anticoagulant, contributes significantly to the aluminum load of source plasma and therefore to the aluminum content of products such as albumin derived from plasma [ 3 ].

Diatomaceous earth filter aid, as a material used in manufacturing process, also increase aluminum in the solution. Although appropriate procedures of manufac-turing can reduce aluminum in albumin products [ 4 ]. Leaching of aluminum from glass containers during storage has also been reported [ 5 ].

Recently the relationship between aluminum and some diseases, for example, bone disease or nervous disorders in patients on chronic hemodialysis, have drawn much attention. They may be caused by dialysis solutions with a high aluminum level [ 6 - 11 ].

The European Pharmacopoeia monograph specifies that the aluminum concentration in albumin products used for patients on hemodialysis and premature infants shall be 200 μg/L or less. So evaluation of aluminum concentration in albumin product is a basic and useful parameter. Albumin solution is produced by Cohn frac-tionation.

The aim of this study was setting a method for alu-minum measurement in albumin solution (5% and 20%) by atomic absorption spectrometry, using electrothermal atomizer (Graphite Furnace) in Iran for the first time and evaluation the aluminum content in intermediate products, final products and also after 3 months storage these products in glass container, because it is important to determine the aluminum concentration in albumin products for the patients undergoing dialysis or the pre-mature infants.

MATERIALS AND METHODS

Samples were collected from routine fractionation process in albumin production. These fractions were:

1. Primary pooled plasma
2. After dissolution of paste V in buffer solution
3. After ultrafiltration
4. Before Dialysis
5. After dialysis with distilled buffer
6. After concentration of the solution
7. After pH adjustment
8. Final bulk product before filling

Table 1 shows the concentration of aluminum in 8 fractions of 10 batches. The concentration of aluminum in primary plasma was in its highest rate (833.2± 87.11 μg/L). After fractionation the content of alumi-num was decreased about 3 folds (309.8 ± 23 μg/L) and it has been maintained constant in other steps of manu-facturing process. Only concentration can increase alu-minum content in this process (447±17).

Table 2 shows concentration of aluminum in final albumin 20% solution (247 ± 88.7 μg/L) and Table 3 shows concentration of aluminum in albumin 5% (157.5 ± 57.1 μg/L).

The glass containers which are used in the company for the albumin solution were examined for aluminum leakage. They were tested 3 months after the first meas-urement. The results in Table 4 show no significant change in aluminum during this period (215.9 ± 49.9).

DISCUSSION

We have set up a method for aluminum measure-ment in albumin solutions in Iran for the first time.

We also have examined different stages in albumin purification to measure the aluminum concentration in albumin products. The high concentration of aluminum in primary plasma is probably due to the usage of anti-coagulants which may introduce a high level of alumi-num. We found that the aluminum concentration in al-bumin solution is remarkably reduced in fractionation process. Only in one stage the aluminum content has been increased and it is probably due to the filters and other chemicals which are used to adjust pH and elec-trolyte concentration. On the other hand concentration may have an important role in increasing aluminum content in this stage.

The content of aluminum in final products in most cases is lower than that stated in European Pharmaco-poeia. They have recommended that not more than 200 μg/L must be measured, if the albumin solution is in-tended for administration to patients under dialysis or to premature infants, and otherwise it must be mentioned on the label.

Storage of albumin products in glass containers used in Iran has no significant effect on aluminum concentra-tion in albumin products during storage and therefore they are recommended for further use.

REFERENCES

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