Stability of L-asparaginase: an enzyme used in leukemia treatment.
L-asparaginase from Escherichia coli is an important enzyme widely used in leukemia treatment under the trade name Elspar. Up to now, however, the aspects of its stability and storage has not been studied in detail. The aim of this work is to analyze the factors that could interfere in the enzyme's stability. The enzymatic activity was found to be stable in wide pH range (4.5-11.5), showing a slight increase in activity and stability in alkaline pHs, which indicates a more stable conformation of the molecule. The enzyme proved to have a high activity restoration capacity when submitted to temperatures of 65 degrees C, in pH 8.6 buffer and, surprisingly, in physiologic solution. This suggests a positive effect of sodium ions on such restoration capacity. Stability was high in different diluents used as parenteral solutions and in recipients used in medical practice without significant loss of activity for at least 7 days. These results lead us to conclude that the enzyme has a high stability after the lyophilized form has been reconstituted (at least 7 days), since the necessary precautions are taken in terms of sterile manipulation and if it is stored in a suitable parenteral vehicle under low temperature (about 8 degrees C).
Stecher
A L
AL
Department of Biochemical and Pharmaceutical Technology, Pharmaceutical Sciences School, University of São Paulo, Brazil.
de Deus
P M
PM
Polikarpov
I
I
Abrahão-Neto
J
J
D000970:Antineoplastic Agents / Q000737:chemistry*; D001215:Asparaginase / Q000737:chemistry*; D004795:Enzyme Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007938:Leukemia / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001215:Asparaginase