A Radioimmunoassay for the Anticonvulsant and Neuroprotective Agent, MK-801%

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Abstract
A radioimmunoassay is described for MK-801, a potent anticon-vulsant and neuroprotective agent. Two immunogens were prepared from N-glutaryl- and N-carboxyethyl-MK-801 by coupling through their carboxyl groups to bovine serum albumin. Radioligands were 1-125-iodotyramine conjugates of the same derivatives. Both types of antisera displayed bridge recognition which could be circumvented. In the first case, specificity for N-acyl derivatives was satisfied by acetylating the analyte prior to measurement. Antisera to the N-alkyl derivative yielded a satisfactory assay for MK-801 when the heterologous radioligand was employed. The first of these strategies was adopted for the routine assay. Specificity relative to hydroxylated metabolites was a function both of antiserum selectivity and sample preparation. High plasma concentrations of drugs concomitantly administered to epileptics posed special analytical problems. Assay sensitivity is 40 pg/ml in plasma and the interassay CV is about 5%.