Kensler T W, Jayaram H N, Cooney D A
J Biochem Biophys Methods. 1980 Jan-Feb;2(1):29-35. doi: 10.1016/0165-022x(80)90071-8.
A sensitive radiometric enzyme-inhibition assay is described for the determination of N-phosphonacetyl-L aspartic acid (PALA, NSC-224,131) in plasma. The assay is based on the inhibition of PALA, at low concentrations of the competitive co-substrate carbamyl phosphate, of L-aspartate transcarbamylase prepared from mouse spleen. The assay responds with good reproducibility and in a proportional way to concentrations of PALA over the range of 2-20 nM; as such, it represents a 100-fold increase in sensitivity over existing methodologies. The applicability and pertinence of this assay to long-term pharmacokinetic studies with PALA is demonstrated by the one month persistence of nanomolar concentrations of PALA in the plasma of mice treated with a single dose of the drug.
