A radioreceptor assay in which iodocyanopindolol is used to determine propranolol and its active metabolites in unextracted serum or plasma.

This rapid, sensitive, simple radioreceptor assay (RRA) for l-propranolol and its active metabolites in unextracted samples requires 5 microL of sample, a beta-adrenergic antagonist, 125-l-labeled (-)cyanopindolol (125ICYP), and turkey erythrocyte membrane receptors (Kd = 40 pmol/L). Equal volumes (100 microL) of diluted sample and 125ICYP are incubated with 500 microL of erythrocyte membranes for 30 min. Cold isotonic saline (2.5 mL) is added, and the mixture is centrifuged. The concentration of drug that inhibited receptor binding by 50% (IC50) was l-propranolol, 1.5 micrograms/L; d-propranolol, 243 micrograms/L; and 4-hydroxypropranolol, 8.8 micrograms/L. Analytical recovery of propranolol added to serum was 93 to 120%; results for 138 clinical samples tested by this method and by liquid chromatography correlated well (r = 0.96). Results correlated strongly (r = 0.98) for 23 clinical samples tested by RRA and analyzed for both propranolol and 4-hydroxypropranolol by liquid chromatography. The sensitivity of this RRA was 0.3 micrograms/L, and both intra- and interassay CVs were less than 12%. Modifications of this method could permit testing of other nonselective beta-blockers.