Modification of the radioreceptor assay technique for estimation of serum neuroleptic drug levels leads to improved precision and sensitivity.

This report describes a series of modifications in the radioreceptor assay procedure for monitoring of serum neuroleptic levels which resulted in a substantial increase in precision and in a higher sensitivity than is the case with existing assays. The use of a dopamine receptor preparation from pig striatum yielded a lower limit of sensitivity for haloperidol of 0.08 ng/ml, when 0.5 ml serum was used in the assay; the intra- and inter-assay coefficients of variation were 3 and 9%, respectively. The relative antipsychotic potency of various neuroleptics correlated with their optimal daily dosage. Anticonvulsants (carbamazepine, phenytoin, barbiturates), anxiolytics (diazepam, bromazepam), as well as other drugs or hormones such as lithium, chloral hydrate, L-tryptophan or L-thyroxine did not interfere with the assay. Simultaneous determination of haloperidol by the radioreceptor assay and radioimmunoassay in serum showed good correlation (r = 0.994). Good correlation was also noted between the average optimal clinical daily dose of the neuroleptics and their affinity to the dopamine receptor of the porcine striatum (r = 0.891). Cross-laboratory assessment indicated good correlation between the estimation of haloperidol by a dopamine receptor preparation from bovine caudata and porcine striata (r = 0.830). The sensitivity of the present assay was improved about 30-fold compared to those previously reported.