Determination of chlorpromazine in serum by radioreceptor assay and HPLC

SUMMARY. A radioreceptor assay for chlorpromazine in serum, which is based on binding to dopamine receptors, is described. This method has been postulated to measure all active metabolites as well as the parent drug. We have compared this method with an HPLC method for chlorpromazine. Dopamine-blocking activity, measured in serum samples from schizophrenic patients receiving chlorpromazine, was 1·85-9·1 times higher than serum chlorpromazine level measured by HPLC. The correlation between the two methods was 0·75. Dopamine-blocking activity was related more closely to dose of drug and to serum prolactin level than was serum chlorpromazine level measured by HPLC. Monitoring of therapeutic drug levels has proved particularly useful in areas where long-term maintenance therapy is involved, e.g. in the use of anticonvulsants, theophylline and lithium. One such field in which maintenance therapy is given long term, often for life, but in which there is very little knowledge of benefit, is schizophrenia. The neuroleptic drugs that are used to reduce acute symptoms are given subsequently for prolonged periods in order to prevent relapse, with little idea of the dosage required to do so in any given patient. Severe, occasionally irreversible, side effects are also associated with these drugs. It would be useful, therefore, to investigate whether a therapeutic and/or toxic range of blood levels can be found which would enable drug level monitoring to help rationalise therapy. Ideally, since neuroleptics act centrally, drug concentrations in the CSF should be measured, However, as this could not be done routinely, the best alternative is to measure drug concen-trations in blood. Many of these drugs, notably the phenothiazines, have active metabolites; thus, the concentration of the parent compound may be only poorly related to the clinical or side effects