MEASUREMENT OF L-ASPARAGINE (ASN) LEVELS IN THE PRESENCE OF E. COLI L-ASPARAGINASE (ASNASE) IS IMPROVED BY THE USE OF ASPARTIC β SEMIALDEHYDE (ASA)

Abstract

The anti-leukemic activity of ASNase is thought to result from depletion of serum ASN. In studies of the pharmacologic effects of ASNase, investigators have reported dramatic prolonged reduction in the serum concentration of ASN after the administration of ASNase. Such measurements, however, have not accounted for the problem of hydrolysis of ASN by ASNase that is present in blood samples. We examined recovery of 14C ASN from blood samples with and without added ASNase at various concentrations. In the presence of ≥0.001 IU/ml of ASNase, the amount of 14C ASN recovered was 90% of control. Blood samples drawn from patients at 1 and 7 days following ASNase injection were collected directly into tubes containing 14C ASN +/- ASA. Recovery with ASA, was 60-110% and 100-110% of control (i.e., no ASNase) on days 1 and 7 respectively. We conclude that: 1) continued hydrolysis of ASN by ASNase can result in falsely low serum ASN measurements; 2) ASA is a potent inhibitor of E. Coli ASNase; 3) ASA present in collection tubes obviates the problem of continued ASNase activity. Thus, for accurate measurements of the rate and degree of ASN depletion by ASNase, ASA should be present in the blood collection system.